核microRNA9介导TGF-β诱导转录过程中G-四链体的形成和3D基因组的组织-动脉网

Nuclear microRNA 9 mediates G-quadruplex formation and 3D genome organization during TGF-β-induced transcription

Nature 等信源发布 2024-12-20 23:41

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AbstractThe dynamics of three-dimensional (3D) genome organization are essential to transcriptional regulation. While enhancers regulate spatiotemporal gene expression, chromatin looping is a means for enhancer-promoter interactions yielding cell-type-specific gene expression. Further, non-canonical DNA secondary structures, such as G-quadruplexes (G4s), are related to increased gene expression.

摘要三维（3D）基因组组织的动态对转录调控至关重要。虽然增强子调节时空基因表达，但染色质环是增强子-启动子相互作用产生细胞类型特异性基因表达的手段。此外，非经典DNA二级结构，例如G-四联体（G4s），与基因表达增加有关。

However, the role of G4s in promoter-distal regulatory elements, such as super-enhancers (SE), and in chromatin looping has remained elusive. Here we show that mature microRNA 9 (miR-9) is enriched at promoters and SE of genes that are inducible by transforming growth factor beta 1 (TGFB1) signaling.

然而，G4s在启动子远端调控元件（例如超级增强子（SE））和染色质环中的作用仍然难以捉摸。在这里，我们显示成熟的microRNA 9（miR-9）富含通过转化生长因子β1（TGFB1）信号传导诱导的基因的启动子和SE。

Moreover, we find that miR-9 is required for formation of G4s, promoter-super-enhancer looping and broad domains of the euchromatin histone mark H3K4me3 at TGFB1-responsive genes. Our study places miR-9 in the same functional context with G4s and promoter-enhancer interactions during 3D genome organization and transcriptional activation induced by TGFB1 signaling, a critical signaling pathway in cancer and fibrosis..

此外，我们发现miR-9是在TGFB1反应基因上形成G4s，启动子超增强子环和常染色质组蛋白标记H3K4me3的广泛结构域所必需的。我们的研究将miR-9与G4s和启动子-增强子相互作用置于相同的功能背景下，在3D基因组组织和TGFB1信号诱导的转录激活过程中，TGFB1信号是癌症和纤维化的关键信号通路。。

IntroductionThe nuclear genome in eukaryotic cells consists of DNA molecules packaged into thread-like structures known as chromosomes, which are built of chromatin. Thus, chromatin is the physiological template for biological processes in the nucleus of eukaryotic cells. Studying how chromatin is folded inside the cell nucleus and its dynamic three-dimensional (3D) structure is essential to understanding these biological processes comprising transcription, RNA-splicing, -processing, -editing, DNA-replication, -recombination, and -repair.

引言真核细胞的核基因组由DNA分子组成，这些DNA分子被包装成线状结构，称为染色体，由染色质构成。因此，染色质是真核细胞细胞核生物过程的生理模板。研究染色质如何在细胞核内折叠及其动态三维（3D）结构对于理解这些生物过程至关重要，这些生物过程包括转录，RNA剪接，加工，编辑，DNA复制，重组和修复。

The chromatin is hierarchically organized at different levels including chromosomal territories, compartments, and self-interacting topologically associating domains, altogether giving rise to a highly dynamic 3D genome organization1. Remarkably, the structure of the genome is intrinsically linked to its function as shown by extensive correlations between chromatin condensation and related gene transcription.

染色质在不同水平上分层组织，包括染色体区域，区室和自相互作用的拓扑关联域，共同产生高度动态的3D基因组组织1。值得注意的是，染色质浓缩和相关基因转录之间的广泛相关性表明，基因组的结构与其功能有着内在的联系。

For example, chromatin shows condensed regions, referred to as heterochromatin (by convention, transcriptionally “inactive”), and less condensed regions, referred to as euchromatin (transcriptionally “active”). Transcriptional regulation directly corresponds to the mechanisms of how chromatin may be structurally arranged rendering it accessible to the transcription machinery2.

例如，染色质显示浓缩区域，称为异染色质（按惯例，转录“无活性”），浓缩程度较低的区域，称为常染色质（转录“活性”）。转录调控直接对应于染色质如何在结构上排列的机制，使其可被转录机器访问2。

These mechanisms regulating chromatin structure and transcription involve histone modifications, histone deposition, nucleosome remodeling, DNA methylation, non-coding RNAs (ncRNA), and secondary structures of nucleic acids, among others3,4,5,6,7. In addition, an increasing number of recent publications based on integrative analysis of multi-omics studies implementing next-generation sequencing (NGS) technologies, chromosome conformation capture-based method.

这些调节染色质结构和转录的机制涉及组蛋白修饰，组蛋白沉积，核小体重塑，DNA甲基化，非编码RNA（ncRNA）和核酸二级结构等3,4,5,6,7。此外，越来越多的最新出版物基于对实施下一代测序（NGS）技术的多组学研究的综合分析，即基于染色体构象捕获的方法。

MiR-9 is required for H3K4me3 broad domains at promoters, basal transcriptional activity, and G-quadruplex formationTo further investigate a potential role of nuclear miR-9 in transcription regulation, we performed a sequencing experiment following Cleavage Under Targets and Tagmentation (CUT&Tag) for high-resolution, genome-wide profiling of tri-methylated lysine 4 of histone 3 (H3K4me3) in MLg and MLE-12 cells that were transiently transfected with Ctrl or miR-9-specific antagomiR to induce a miR-9-LOF (Fig. 2a−e, Supplementary Fig. 3a−d).

MiR-9是启动子上H3K4me3广泛结构域，基础转录活性和G-四链体形成所必需的为了进一步研究核MiR-9在转录调控中的潜在作用，我们在靶标切割和标记（切割和标记）后进行了测序实验，用于在用Ctrl或MiR-9特异性antagomiR瞬时转染以诱导MiR-9-LOF的MLg和MLE-12细胞中高分辨率，全基因组分析组蛋白3（H3K4me3）的三甲基化赖氨酸4（图2a-e，补充图3a-d）。

Peak distribution analysis of the H3K4me3 CUT&Tag showed that 60.8% (P = 0.01) of the H3K4me3 broad domains in Ctrl transfected MLg cells were enriched with miR-9 (Fig. 2a), whereas 63% (P < 0.01) of the H3K4me3 broad domains were enriched with miR-9 in Ctrl transfected MLE-12 cells (Supplementary Fig. 3b).

H3K4me3切割标签的峰分布分析显示，Ctrl转染的MLg细胞中60.8%（P=0.01）的H3K4me3宽域富含miR-9（图2a），而63%（P < 0.01) 在Ctrl转染的MLE-12细胞中，H3K4me3的广泛结构域中富含miR-9（补充图3b）。

Interestingly, H3K4me3 levels at broad domains were significantly reduced in MLg cells from a median of 1.6 RPKM (IQR = 3.3) in Ctrl transfected cells to a median of 0.8 RPKM (IQR = 1.8; P = 0.002) following miR-9-LOF (Fig. 2b, top), whereas the effects of miR-9-LOF in MLE-12 cells were not significant (Fig. 2b, bottom).

有趣的是，MLg细胞中广泛结构域的H3K4me3水平从Ctrl转染细胞的中位数1.6 RPKM（IQR=3.3）显着降低至中位数0.8 RPKM（IQR=1.8；miR-9-LOF后（图2b，顶部），而miR-9-LOF在MLE-12细胞中的作用不显着（图2b，底部）。

In addition, we observed that the loci of the H3K4me3 broad domains with miR-9 enrichment were different in MLg and MLE-12 cells (Supplementary Fig. 3c, d), confirming that miR-9 regulates different genes in these two cell lines. Due to these results and the higher levels of nuclear miR-9 (Fig. 1b), we focused on MLg cells.

此外，我们观察到具有miR-9富集的H3K4me3宽结构域的基因座在MLg和MLE-12细胞中是不同的（补充图3c，d），证实miR-9调节这两种细胞系中的不同基因。由于这些结果和较高水平的核miR-9（图1b），我们专注于MLg细胞。

Further peak distribution analysis showed that H3K4me3 broad domains were reduced from 27.6% in Ctrl transfected MLg cells to 22.1% after miR-9-LOF, whereas medium and narrow H3K4me3 domains increased (Fig. 2c). Interestingly, the shift from H3K4me3 broad domains to medium and narrow domains f.

进一步的峰分布分析显示，miR-9-LOF后，H3K4me3宽结构域从Ctrl转染的MLg细胞中的27.6%降低至22.1%，而中等和窄H3K4me3结构域增加（图2c）。有趣的是，从H3K4me3宽域转变为中等和窄域f。

To further elucidate the biological relevance of our findings we performed GSEA44 on the loci with miR-9 enrichment and nascent RNA as determined by miR-9 ChIRP-seq and GRO-seq, respectively (Fig. 7a, b). We found significant enrichment of genes related to the categories “TGFB cell response” (P = 7.55E-09), “TGFB” (P = 2.61E-08), “Cell proliferation” (P = 4.66E-08), and “Fibroblasts proliferation” (P = 1.61E-07), suggesting an involvement of the loci with miR-9 enrichment and nascent RNA in these biological processes.

为了进一步阐明我们研究结果的生物学相关性，我们分别通过miR-9 ChIRP-seq和GRO-seq测定了miR-9富集和新生RNA的基因座上的GSEA44（图7a，b）。我们发现与“TGFB细胞反应”（P=7.55E-09），“TGFB”（P=2.61E-08），“细胞增殖”（P=4.66E-08）和“成纤维细胞增殖”（P = 1.61E-07），表明该基因座与miR-9富集和新生RNA参与了这些生物过程。

Supporting these observations, RNA FISH and immunostaining in MLg cells showed that TGFB1 treatment increased the levels of miR-9, G4 and H3K4me3 in miR-9-dependent manner (Fig. 7c, d). Similarly as in IPF hLF (Supplementary Fig. 1d), the majority of miR-9 was detected in the cell nucleus of MLg cells after TGFB1 treatment.

支持这些观察结果，MLg细胞中的RNA FISH和免疫染色显示TGFB1处理以miR-9依赖性方式增加了miR-9，G4和H3K4me3的水平（图7c，d）。与IPF hLF（补充图1d）类似，在TGFB1处理后，在MLg细胞的细胞核中检测到大多数miR-9。

Interestingly, we detected significantly increased enrichment of miR-9 at promoters of miR-9 target genes after TGFB1 treatment in MLg cells that were analyzed by qPCR after ChIRP using miR-9-specific biotinylated antisense oligonucleotides (Fig. 7e). These results were complemented by H3K4me3 ChIP-seq in MLg cells that were transiently transfected with Ctrl or miR-9-specific antagomiR probes, and non-treated or treated with TGFB1 (Fig. 7f−h and Supplementary Fig. 8a−c).

有趣的是，我们检测到在使用miR-9特异性生物素化反义寡核苷酸进行ChIRP后通过qPCR分析的MLg细胞中TGFB1处理后miR-9靶基因启动子处miR-9的富集显着增加（图7e）。这些结果得到了用Ctrl或miR-9特异性antagomiR探针瞬时转染的MLg细胞中H3K4me3 ChIP-seq的补充，并且未经处理或用TGFB1处理（图7f-h和补充图8a-c）。

H3K4me3 levels significantly increased after TGFB1 treatment at promoters of TGFB-responsive genes in miR-9-dependent manner (Fig. 7f, left). These effects were not observed at the promoters of genes that did not respond to TGFB1 treatment (Fig. 7f, right) supporting the specificity of the effects observed.

TGFB1处理后，TGFB反应基因启动子的H3K4me3水平以miR-9依赖性方式显着增加（图7f，左）。在对TGFB1处理无反应的基因的启动子上未观察到这些作用（图7f，右），这支持了观察到的作用的特异性。

By checking on H3K4me3 levels at loci, in which we detected G4s by CUT&Tag, we observed that TGFB1 did not significantly affect H3K4me3 levels, whereas the combinati.

通过检查基因座上的H3K4me3水平，我们通过CUT＆Tag检测到G4s，我们观察到TGFB1对H3K4me3水平没有显着影响，而组合。

To find enhancer and Super-Enhancer, the Program Rank Ordering of Super-Enhancer (ROSE) was used (default settings). To determine the potential super-enhancer marked or not marked by miR-9, we crossed the miR-9 ChIRP-seq, with the output results from ROSE of H3K27ac peaks from MLg Ctrl cells using bedtools intersect.

为了找到增强子和超级增强子，使用了超级增强子（ROSE）的程序等级排序（默认设置）。为了确定miR-9标记或未标记的潜在超增强子，我们将miR-9 ChIRP-seq杂交，使用bedtools intersect从MLg Ctrl细胞的H3K27ac峰的ROSE输出结果。

If at least a peak of miR-9 overlap with an H3K27ac peak that type of enhancer will be considered as marked by miR-9. overlap with H3K27ac.All ChIP-seq and miR-9 ChIRP-seq were quantified from the center of both Peak list by the help of annotatePeaks from HOMER with the settings: annotatePeaks.pl list.bed mm10 -size 4000 -norm 1,000,000 -hist 10 -d maketagLib_Samples > output_quanty.txt.

如果miR-9的至少一个峰与H3K27ac峰重叠，则该类型的增强子将被认为是由miR-9标记的。与H3K27ac重叠。所有ChIP-seq和miR-9 ChIRP-seq都是在HOMER的annotatePeaks的帮助下从两个峰列表的中心进行量化的，设置为：annotatePeaks.pl list.bed mm10-size 4000-norm 1000000-hist 10-d maketagLib\u Samples>output\u quanty.txt。

The results of this command were used as input in a custom R-script to produce the aggregate plots to normalized by Z-score of the enrichment of the protein on the type of enhancer area by the help of a custom Script in R. (https://github.com/jcorderJC12/001nuMir9_G4_3D).Chromatin immunoprecipitation (ChIP)ChIP analysis was performed as described earlier5,67 with minor adaptations.

该命令的结果被用作自定义R脚本中的输入，以产生聚集图，通过R中的自定义脚本的帮助，通过增强子区域类型上蛋白质富集的Z分数进行归一化(https://github.com/jcorderJC12/001nuMir9_G4_3D)。如前所述进行染色质免疫沉淀（ChIP）ChIP分析5,67，稍作修改。

Briefly, cells were cross-linked with 1% methanol-free formaldehyde (ThermoFisher Scientific) lysed, and sonicated with Diagenode Bioruptor to an average DNA length of 300–600 bp. After centrifugation, the soluble chromatin was immunoprecipitated with 3 µg of antibodies specific for H3K4me3 (Abcam, # ab8580), DNA G-quadruplex structures, clone BG4 (Millipore, # MABE917), and IgG (Santa Cruz, #sc-2027).

简而言之，将细胞与1%无甲醇甲醛（ThermoFisher Scientific）交联裂解，并用Diagenode Bioruptor超声处理至平均DNA长度为300-600bp。离心后，用3μg对H3K4me3（Abcam，#ab8580），DNA g-四链体结构，克隆BG4（Millipore，#MABE917）和IgG（Santa Cruz，#sc-2027）特异的抗体免疫沉淀可溶性染色质。

Reverse crosslinked immunoprecipitated chromatin was purified using the QIAquick PCR purification kit (Qiagen) and subjected to ChIP-quantitative PCR. The primer pairs used for gene promoter and super-enhancer regions are described in the Supplementary Table 2.Chromatin RNA immunoprecipitationChrom.

使用QIAquick PCR纯化试剂盒（Qiagen）纯化反向交联的免疫沉淀染色质，并进行ChIP定量PCR。用于基因启动子和超增强子区域的引物对在补充表2中描述。染色质RNA免疫沉淀Chrom。

Data availability

数据可用性

The data supporting the findings of this study are available from the corresponding authors upon request. Source data are provided with this paper as a Source Data file. The sequencing data generated in this study have been deposited in NCBI’s Gene Expression Omnibus database75 under accession number GSE244952.

支持本研究结果的数据可应要求从通讯作者处获得。本文提供了源数据作为源数据文件。本研究中产生的测序数据已保存在NCBI的基因表达综合数据库75中，登录号为GSE244952。

Furthermore, we retrieved and used publicly available datasets to aid analysis of our data. Supplementary Data 1 contains all data sets used in this study. The model in Fig. 9d was Created with BioRender.com. Regarding the mass spectrometry-based proteomic, the full list of settings can be found in the “report.log.txt”, full code for data processing and statistical analysis can be found in “stat-mir9-001.zip” uploaded along with the mass spectrometric raw data to the ProteomeXchange Consortium with dataset identifier: PXD054375, via the MassIVE partner repository (https://massive.ucsd.edu/, MassIVE-ID: MSV000095480; https://doi.org/10.25345/C5639KH31:). Source data are provided with this paper..

此外，我们检索并使用公开可用的数据集来帮助分析我们的数据。补充数据1包含本研究中使用的所有数据集。图9d中的模型是使用BioRender.com创建的。关于基于质谱的蛋白质组学，完整的设置列表可以在“report.log.txt”中找到，数据处理和统计分析的完整代码可以在“stat-mir9-001.zip”中找到，它与质谱原始数据一起通过MassIVE partner repository上传到ProteomeXchange Consortium，数据集标识符为PXD054375(https://massive.ucsd.edu/，海量ID:MSV000095480；https://doi.org/10.25345/C5639KH31:)。本文提供了源数据。。

ReferencesJerkovic, I. & Cavalli, G. Understanding 3D genome organization by multidisciplinary methods. Nat. Rev. Mol. Cell Biol. 22, 511–528 (2021).Article

参考文献Jerkovic，I。＆Cavalli，G。通过多学科方法理解3D基因组组织。Nat。Rev。Mol。Cell Biol。。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Misteli, T. The self-organizing genome: principles of genome architecture and function. Cell 183, 28–45 (2020).Article

Misteli，T。自组织基因组：基因组结构和功能的原理。细胞183,28-45（2020）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Gohlke, J. et al. DNA methylation mediated control of gene expression is critical for development of crown gall tumors. PLoS Genet. 9, e1003267 (2013).Article

Gohlke，J。等人。DNA甲基化介导的基因表达控制对于冠瘿肿瘤的发展至关重要。PLoS Genet。9，e1003267（2013）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Georgakopoulos-Soares, I., Morganella, S., Jain, N., Hemberg, M. & Nik-Zainal, S. Noncanonical secondary structures arising from non-B DNA motifs are determinants of mutagenesis. Genome Res. 28, 1264–1271 (2018).Article

。基因组研究281264-1271（2018）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Dobersch, S. et al. Positioning of nucleosomes containing gamma-H2AX precedes active DNA demethylation and transcription initiation. Nat. Commun. 12, 1072 (2021).Article

Dobersch，S。等人。含有γ-H2AX的核小体的定位先于活性DNA去甲基化和转录起始。国家公社。121072（2021）。文章

ADS

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Singh, I. et al. MiCEE is a ncRNA-protein complex that mediates epigenetic silencing and nucleolar organization. Nat. Genet. 50, 990–1001 (2018).Article

Singh，I。等人MiCEE是一种ncRNA蛋白复合物，介导表观遗传沉默和核仁组织。纳特·吉内特。50990-1001（2018）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Singh, I. et al. High mobility group protein-mediated transcription requires DNA damage marker gamma-H2AX. Cell Res. 25, 837–850 (2015).Article

Singh，I。等人。高迁移率族蛋白介导的转录需要DNA损伤标记γ-H2AX。Cell Res.25837–850（2015）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Papantonis, A. & Cook, P. R. Genome architecture and the role of transcription. Curr. Opin. Cell Biol. 22, 271–276 (2010).Article

Papantonis，A。＆Cook，P.R。基因组结构和转录的作用。货币。奥平。细胞生物学。22271-276（2010）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Jha, R. K., Levens, D. & Kouzine, F. Mechanical determinants of chromatin topology and gene expression. Nucleus 13, 94–115 (2022).Article

Jha，R.K.，Levens，D。＆Kouzine，F。染色质拓扑结构和基因表达的机械决定因素。核13,94-115（2022）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Zaugg, J. B. et al. Current challenges in understanding the role of enhancers in disease. Nat. Struct. Mol. Biol. 29, 1148–1158 (2022).Article

Zaugg，J.B.等人。目前在理解增强子在疾病中的作用方面面临的挑战。自然结构。分子生物学。291148-1158（2022）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Whyte, W. A. et al. Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell 153, 307–319 (2013).Article

Whyte，W.A.等人掌握了转录因子和介体，在关键的细胞身份基因上建立了超级增强子。细胞153307-319（2013）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Hnisz, D. et al. Super-enhancers in the control of cell identity and disease. Cell 155, 934–947 (2013).Article

Hnisz，D。等人。控制细胞特性和疾病的超级增强子。细胞155934-947（2013）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Khan, A. & Zhang, X. dbSUPER: a database of super-enhancers in mouse and human genome. Nucleic Acids Res. 44, D164–D171 (2016).Article

Khan，A。＆Zhang，X。dbSUPER：小鼠和人类基因组中超级增强子的数据库。核酸研究44，D164-D171（2016）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Hsieh, T. S. et al. Enhancer-promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1. Nat. Genet. 54, 1919–1932 (2022).Article

Hsieh，T。S。等人。增强子-启动子相互作用和转录在CTCF，cohesin，WAPL或YY1急性丧失时基本上得以维持。纳特·吉内特。541919-1932（2022）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Varshney, D., Spiegel, J., Zyner, K., Tannahill, D. & Balasubramanian, S. The regulation and functions of DNA and RNA G-quadruplexes. Nat. Rev. Mol. Cell Biol. 21, 459–474 (2020).Article

Varshney，D.，Spiegel，J.，Zyner，K.，Tannahill，D。和Balasubramanian，S。DNA和RNA G-四链体的调节和功能。Nat。Rev。Mol。Cell Biol。21459-474（2020）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Henderson, E., Hardin, C. C., Walk, S. K., Tinoco, I. Jr. & Blackburn, E. H. Telomeric DNA oligonucleotides form novel intramolecular structures containing guanine-guanine base pairs. Cell 51, 899–908 (1987).Article

Henderson，E.，Hardin，C.C.，Walk，S.K.，Tinoco，I.Jr。＆Blackburn，E.H。端粒DNA寡核苷酸形成含有鸟嘌呤-鸟嘌呤碱基对的新型分子内结构。细胞51899-908（1987）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Hansel-Hertsch, R. et al. G-quadruplex structures mark human regulatory chromatin. Nat. Genet. 48, 1267–1272 (2016).Article

Hansel-Hertsch，R。等人。G-四链体结构标记人类调节染色质。纳特·吉内特。481267-1272（2016）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Zheng, K. W. et al. Detection of genomic G-quadruplexes in living cells using a small artificial protein. Nucleic Acids Res. 48, 11706–11720 (2020).Article

Zheng，K.W.等人。使用一种小的人工蛋白质检测活细胞中的基因组G-四链体。核酸研究4811706-11720（2020）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Renciuk, D. et al. G-quadruplex formation in the Oct4 promoter positively regulates Oct4 expression. Biochim. Biophys. Acta Gene Regul. Mech. 1860, 175–183 (2017).Article

Renciuk，D。等人，Oct4启动子中的G-四链体形成正向调节Oct4表达。生物化学。生物物理。Acta基因调控。机械。。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Lago, S. et al. Promoter G-quadruplexes and transcription factors cooperate to shape the cell type-specific transcriptome. Nat. Commun. 12, 3885 (2021).Article

Lago，S。等人。启动子G-四联体和转录因子协同形成细胞类型特异性转录组。国家公社。。文章

ADS

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Esnault, C. et al. G4access identifies G-quadruplexes and their associations with open chromatin and imprinting control regions. Nat. Genet. 55, 1359–1369 (2023).Article

。纳特·吉内特。551359-1369（2023）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Esnault, C. et al. G-quadruplexes are promoter elements controlling nucleosome exclusion and RNA polymerase II pausing. bioRxiv, 2023.02.24.529838 (2023).Agarwal, T., Roy, S., Kumar, S., Chakraborty, T. K. & Maiti, S. In the sense of transcription regulation by G-quadruplexes: asymmetric effects in sense and antisense strands.

Esnault，C。等人，G-四链体是控制核小体排斥和RNA聚合酶II暂停的启动子元件。bioRxiv，2023.02.24.529838（2023）。Agarwal，T.，Roy，S.，Kumar，S.，Chakraborty，T.K。＆Maiti，S。在G-四链体的转录调控意义上：有义和反义链的不对称效应。

Biochemistry 53, 3711–3718 (2014).Article .

生物化学533711-3718（2014）。文章。

CAS

中科院

PubMed

Google Scholar

谷歌学者

Holder, I. T. & Hartig, J. S. A matter of location: influence of G-quadruplexes on Escherichia coli gene expression. Chem. Biol. 21, 1511–1521 (2014).Article

Holder，I.T。＆Hartig，J.S。位置问题：G-四链体对大肠杆菌基因表达的影响。化学。生物学211511-1521（2014）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Consortium, E. P. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57–74 (2012).Article

Consortium，E.P。人类基因组中DNA元素的综合百科全书。《自然》489,57-74（2012）。文章

ADS

Google Scholar

谷歌学者

Quinn, J. J. & Chang, H. Y. Unique features of long non-coding RNA biogenesis and function. Nat. Rev. Genet. 17, 47–62 (2015).Article

。Genet自然Rev。17,47-62（2015）。文章

Google Scholar

谷歌学者

Rubio, K., Castillo-Negrete, R. & Barreto, G. Non-coding RNAs and nuclear architecture during epithelial-mesenchymal transition in lung cancer and idiopathic pulmonary fibrosis. Cell Signal. 70, 109593 (2020).Article

Rubio，K.，Castillo-Negrete，R。＆Barreto，G。肺癌和特发性肺纤维化上皮-间质转化过程中的非编码RNA和核结构。细胞信号。70109593（2020）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Filipowicz, W., Bhattacharyya, S. N. & Sonenberg, N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat. Rev. Genet. 9, 102–114 (2008).Article

Filipowicz，W.，Bhattacharyya，S.N。和Sonenberg，N。microRNA转录后调控的机制：答案在望吗？Genet自然Rev。9102-114（2008）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Park, C. W., Zeng, Y., Zhang, X., Subramanian, S. & Steer, C. J. Mature microRNAs identified in highly purified nuclei from HCT116 colon cancer cells. RNA Biol. 7, 606–614 (2010).Article

Park，C.W.，Zeng，Y.，Zhang，X.，Subramanian，S。＆Steer，C.J。在来自HCT116结肠癌细胞的高度纯化的细胞核中鉴定出成熟的microRNA。RNA生物学。7606-614（2010）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Rasko, J. E. & Wong, J. J. Nuclear microRNAs in normal hemopoiesis and cancer. J. Hematol. Oncol. 10, 8 (2017).Article

Rasko，J.E。＆Wong，J.J。正常造血和癌症中的核microRNA。J、血液学。Oncol公司。10,8（2017）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Huang, V. Endogenous miRNAa: miRNA-Mediated Gene Upregulation. Adv. Exp. Med. Biol. 983, 65–79 (2017).Article

Huang，V。内源性miRNA:miRNA介导的基因上调。高级实验医学生物学。983,65-79（2017）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Leucci, E. et al. microRNA-9 targets the long non-coding RNA MALAT1 for degradation in the nucleus. Sci. Rep. 3, 2535 (2013).Article

Leucci，E。等人。microRNA-9靶向长的非编码RNA MALAT1以在细胞核中降解。科学。第32535页（2013年）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Hwang, H. W., Wentzel, E. A. & Mendell, J. T. A hexanucleotide element directs microRNA nuclear import. Science 315, 97–100 (2007).Article

Hwang，H.W.，Wentzel，E.A。和Mendell，J.T。六核苷酸元件指导microRNA核输入。科学315,97-100（2007）。文章

ADS

CAS

中科院

PubMed

Google Scholar

谷歌学者

Yuva-Aydemir, Y., Simkin, A., Gascon, E. & Gao, F. B. MicroRNA-9: functional evolution of a conserved small regulatory RNA. RNA Biol. 8, 557–564 (2011).Article

Yuva Aydemir，Y.，Simkin，A.，Gascon，E。＆Gao，F.B。MicroRNA-9：保守的小调节RNA的功能进化。RNA生物学。8557-564（2011）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Coolen, M., Katz, S. & Bally-Cuif, L. miR-9: a versatile regulator of neurogenesis. Front. Cell Neurosci. 7, 220 (2013).Article

。正面。细胞神经科学。7220（2013）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Santovito, D. et al. Noncanonical inhibition of caspase-3 by a nuclear microRNA confers endothelial protection by autophagy in atherosclerosis. Sci. Transl. Med. 12, eaaz2294 (2020).Rubio, K. et al. Inactivation of nuclear histone deacetylases by EP300 disrupts the MiCEE complex in idiopathic pulmonary fibrosis.

Santovito，D。等人。核microRNA对caspase-3的非典型抑制通过动脉粥样硬化中的自噬赋予内皮保护作用。科学。翻译。医学12，eaaz2294（2020）。Rubio，K。等人。EP300使核组蛋白脱乙酰酶失活会破坏特发性肺纤维化中的MiCEE复合物。

Nat. Commun. 10, 2229 (2019).Article .

Nat.普通。102229（2019）。文章。

ADS

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Sze, C. C. et al. Coordinated regulation of cellular identity-associated H3K4me3 breadth by the COMPASS family. Sci. Adv. 6, eaaz4764 (2020).Article

Sze，C.C.等人。COMPASS家族对细胞身份相关H3K4me3宽度的协调调节。科学。Adv.6，eaaz4764（2020）。文章

ADS

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Chen, K. et al. Broad H3K4me3 is associated with increased transcription elongation and enhancer activity at tumor-suppressor genes. Nat. Genet. 47, 1149–1157 (2015).Article

Chen，K。等人。广泛的H3K4me3与肿瘤抑制基因的转录延伸和增强子活性增加有关。纳特·吉内特。471149-1157（2015）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Mahat, D. B., Salamanca, H. H., Duarte, F. M., Danko, C. G. & Lis, J. T. Mammalian heat shock response and mechanisms underlying its genome-wide transcriptional regulation. Mol. Cell 62, 63–78 (2016).Article

Mahat，D.B.，Salamanca，H.H.，Duarte，F.M.，Danko，C.G。＆Lis，J.T。哺乳动物热休克反应及其全基因组转录调控机制。分子细胞62,63-78（2016）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Busslinger, G. A. et al. Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl. Nature 544, 503–507 (2017).Article

Busslinger，G.A。等人。粘着蛋白通过转录，CTCF和Wapl定位在哺乳动物基因组中。自然544503-507（2017）。文章

ADS

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Bedrat, A., Lacroix, L. & Mergny, J. L. Re-evaluation of G-quadruplex propensity with G4Hunter. Nucleic Acids Res. 44, 1746–1759 (2016).Article

Bedrat，A.，Lacroix，L。＆Mergny，J.L。用G4Hunter重新评估G-四链体倾向。核酸研究441746-1759（2016）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Pipier, A. et al. Constrained G4 structures unveil topology specificity of known and new G4 binding proteins. Sci. Rep. 11, 13469 (2021).Article

Pipier，A。等人限制的G4结构揭示了已知和新的G4结合蛋白的拓扑特异性。科学。代表1113469（2021）。文章

ADS

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Mootha, V. K. et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat. Genet. 34, 267–273 (2003).Article

Mootha，V.K.等人，参与氧化磷酸化的PGC-1α反应基因在人类糖尿病中协同下调。纳特·吉内特。34267-273（2003）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Buganim, Y. et al. The developmental potential of iPSCs is greatly influenced by reprogramming factor selection. Cell Stem Cell 15, 295–309 (2014).Article

Buganim，Y。等人。iPSC的发育潜力受重编程因子选择的影响很大。细胞干细胞15295-309（2014）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Chronis, C. et al. Cooperative binding of transcription factors orchestrates reprogramming. Cell 168, 442–459.e20 (2017).Article

Chronis，C。等人。转录因子的协同结合协调了重编程。细胞168442-459.e20（2017）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Jin, W. et al. Animal-eRNAdb: a comprehensive animal enhancer RNA database. Nucleic Acids Res. 50, D46–D53 (2022).Article

Jin，W。等人。动物eRNAdb：一个全面的动物增强子RNA数据库。核酸研究50，D46-D53（2022）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

De Magis, A. et al. DNA damage and genome instability by G-quadruplex ligands are mediated by R loops in human cancer cells. Proc. Natl Acad. Sci. USA 116, 816–825 (2019).Article

De Magis，A。等人。G-四联体配体引起的DNA损伤和基因组不稳定性是由人类癌细胞中的R环介导的。程序。国家科学院。科学。美国116816-825（2019）。文章

ADS

PubMed

Google Scholar

谷歌学者

Lyu, J., Shao, R., Kwong Yung, P. Y. & Elsasser, S. J. Genome-wide mapping of G-quadruplex structures with CUT&Tag. Nucleic Acids Res. 50, e13 (2022).Article

Lyu，J.，Shao，R.，Kwong Yung，P.Y。和Elsasser，S.J。用切割和标签对G-四链体结构进行全基因组定位。核酸研究50，e13（2022）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Skourti-Stathaki, K. & Proudfoot, N. J. A double-edged sword: R loops as threats to genome integrity and powerful regulators of gene expression. Genes Dev. 28, 1384–1396 (2014).Article

Skourti-Stathaki，K。＆Proudfoot，N.J。一把双刃剑：R环威胁基因组完整性和强大的基因表达调控因子。Genes Dev.281384–1396（2014）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Sato, K., Hendrikx, A. G. M. & Knipscheer, P. RNA transcripts suppress G-quadruplex structures through G-loop formation. bioRxiv, 2023.03.09.531892 (2023).Hou, Y., Guo, Y., Dong, S. & Yang, T. Novel Roles of G-quadruplexes on Enhancers in human chromatin. bioRxiv, 2021.07.12.451993 (2021).Li, X.

Sato，K.，Hendrikx，A.G.M。＆Knipscheer，P。RNA转录物通过G环形成抑制G-四链体结构。bioRxiv，2023.03.09.531892（2023）。Hou，Y.，Guo，Y.，Dong，S。＆Yang，T。G-四链体对人类染色质增强子的新作用。bioRxiv，2021.07.12.451993（2021）。。

et al. Inhibition of fatty acid oxidation enables heart regeneration in adult mice. Nature 622, 619–626 (2023).ADS .

抑制脂肪酸氧化可以使成年小鼠的心脏再生。自然622619-626（2023）。广告。

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Benayoun, B. A. et al. H3K4me3 breadth is linked to cell identity and transcriptional consistency. Cell 158, 673–688 (2014).Article

Benayoun，B.A。等人，H3K4me3宽度与细胞身份和转录一致性有关。细胞158673-688（2014）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Syed, V. TGF-beta Signaling in Cancer. J. Cell Biochem. 117, 1279–1287 (2016).Article

Syed，V。癌症中的TGF-β信号传导。J、细胞生物化学。1171279-1287（2016）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Dobersch, S., Rubio, K. & Barreto, G. Pioneer factors and architectural proteins mediating embryonic expression signatures in cancer. Trends Mol. Med. 25, 287−302 (2019).Rubio, K. et al. Non-canonical integrin signaling activates EGFR and RAS-MAPK-ERK signaling in small cell lung cancer.

Dobersch，S.，Rubio，K。＆Barreto，G。先驱因子和结构蛋白介导癌症中的胚胎表达特征。趋势分子医学25287-302（2019）。Rubio，K。等人。非经典整合素信号激活小细胞肺癌中的EGFR和RAS-MAPK-ERK信号传导。

Theranostics 13, 2384–2407 (2023).Article .

Theranostics 132384-2407（2023）。文章。

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Akeson, A. L. et al. Embryonic vasculogenesis by endothelial precursor cells derived from lung mesenchyme. Dev. Dyn 217, 11–23 (2000).Article

Akeson，A.L.等人。源自肺间充质的内皮前体细胞的胚胎血管发生。德文Dyn 217，11-23（2000）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Mehta, A. et al. Validation of Tuba1a as appropriate internal control for normalization of gene expression analysis during mouse lung development. Int. J. Mol. Sci. 16, 4492–4511 (2015).Article

Mehta，A。等人。验证Tuba1a作为小鼠肺发育过程中基因表达分析正常化的适当内部对照。Int.J.Mol.Sci。164492-4511（2015）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Chu, C., Qu, K., Zhong, F. L., Artandi, S. E. & Chang, H. Y. Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. Mol. Cell 44, 667–678 (2011).Article

Chu，C.，Qu，K.，Zhong，F.L.，Artandi，S.E。＆Chang，H.Y。长非编码RNA占据的基因组图谱揭示了RNA-染色质相互作用的原理。分子细胞44667-678（2011）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).Article

Langmead，B。＆Salzberg，S.L。与Bowtie 2快速间隙读取对齐。《自然方法》9357-359（2012）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Zhang, Y. et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 9, R137 (2008).Article

Zhang，Y.等人。ChIP-Seq（MACS）的基于模型的分析。基因组生物学。9，R137（2008）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Heinz, S. et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38, 576–589 (2010).Article

Heinz，S.等人。谱系决定转录因子的简单组合引发巨噬细胞和B细胞身份所需的顺式调控元件。。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ramirez, F., Dundar, F., Diehl, S., Gruning, B. A. & Manke, T. deepTools: a flexible platform for exploring deep-sequencing data. Nucleic Acids Res. 42, W187–W191 (2014).Article

Ramirez，F.，Dundar，F.，Diehl，S.，Grunning，B.A。＆Manke，T。deepTools：探索深度测序数据的灵活平台。核酸研究42，W187–W191（2014）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ji, X., Li, W., Song, J., Wei, L. & Liu, X. S. CEAS: cis-regulatory element annotation system. Nucleic Acids Res. 34, W551–W554 (2006).Article

Ji，X.，Li，W.，Song，J.，Wei，L。＆Liu，X.S。CEAS：顺式调控元件注释系统。核酸研究34，W551–W554（2006）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Machanick, P. & Bailey, T. L. MEME-ChIP: motif analysis of large DNA datasets. Bioinformatics 27, 1696–1697 (2011).Article

Machanick，P。＆Bailey，T。L。MEME芯片：大型DNA数据集的基序分析。生物信息学271696-1697（2011）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Hansel-Hertsch, R., Spiegel, J., Marsico, G., Tannahill, D. & Balasubramanian, S. Genome-wide mapping of endogenous G-quadruplex DNA structures by chromatin immunoprecipitation and high-throughput sequencing. Nat. Protoc. 13, 551–564 (2018).Article

Hansel-Hertsch，R.，Spiegel，J.，Marsico，G.，Tannahill，D。＆Balasubramanian，S。通过染色质免疫沉淀和高通量测序对内源性G-四链体DNA结构进行全基因组定位。自然协议。13551-564（2018）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Kaya-Okur, H. S. et al. CUT&Tag for efficient epigenomic profiling of small samples and single cells. Nat. Commun. 10, 1930 (2019).Article

Kaya Okur，H.S.等人的CUT＆Tag用于小样本和单细胞的有效表观基因组分析。国家公社。101930（2019）。文章

ADS

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Mumbach, M. R. et al. Enhancer connectome in primary human cells identifies target genes of disease-associated DNA elements. Nat. Genet. 49, 1602–1612 (2017).Article

Mumbach，M.R。等人，《原代人类细胞中的增强子连接组》鉴定了与疾病相关的DNA元件的靶基因。纳特·吉内特。491602-1612（2017）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Servant, N. et al. HiC-Pro: an optimized and flexible pipeline for Hi-C data processing. Genome Biol. 16, 259 (2015).Article

Servant，N.等人。HiC Pro：用于Hi-C数据处理的优化且灵活的管道。基因组生物学。16259（2015）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Hughes, C. S. et al. Single-pot, solid-phase-enhanced sample preparation for proteomics experiments. Nat. Protoc. 14, 68–85 (2019).Article

Hughes，C.S.等人。用于蛋白质组学实验的单罐固相增强样品制备。自然协议。14,68-85（2019）。文章

CAS

中科院

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Demichev, V., Messner, C. B., Vernardis, S. I., Lilley, K. S. & Ralser, M. DIA-NN: neural networks and interference correction enable deep proteome coverage in high throughput. Nat. Methods 17, 41–44 (2020).Article

Demichev，V.，Messner，C.B.，Vernardis，S.I.，Lilley，K.S。＆Ralser，M.DIA-NN：神经网络和干扰校正能够在高通量下实现深度蛋白质组覆盖。自然方法17,41-44（2020）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Cox, J. et al. Accurate proteome-wide label-free quantification by delayed normalization and maximal peptide ratio extraction, termed MaxLFQ. Mol. Cell Proteom. 13, 2513–2526 (2014).Article

Cox，J.等人。通过延迟归一化和最大肽比提取（称为MaxLFQ）进行准确的蛋白质组范围内无标记定量。分子细胞蛋白质组学。132513-2526（2014）。文章

CAS

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Google Scholar

谷歌学者

Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).Article

Ritchie，M.E.等人limma为RNA测序和微阵列研究提供了差异表达分析的能力。核酸研究43，e47（2015）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Edgar, R., Domrachev, M. & Lash, A. E. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 30, 207–210 (2002).Article

Edgar，R.，Domrachev，M。＆Lash，A.E。基因表达综合：NCBI基因表达和杂交阵列数据库。核酸研究30207-210（2002）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

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谷歌学者

Download referencesAcknowledgementsWe thank Roswitha Bender and Anne Robert for technical support; Virgine Marchand, Iouri Motorine and the EpiRNA-Seq Core Facility for support with NGS-based methods; Malgorzata Wygrecka, Kerstin Richter, Alessandro Ianni, Sylvain Maenner and Bruno Charpentier for reagents; Dominique Dumas for support with confocal microscopy; Amine Armich, Jean-Baptiste Vincourt, Sylvie Fournel-Gigleux, Mohamed Ouzzine, Sandrine Gulberti, Catherine Bui, Lydia Barré and Nick Ramalanjaona for comments.

下载参考文献致谢我们感谢Roswitha Bender和Anne Robert的技术支持；Virgine Marchand，Iouri Motorine和EpiRNA-Seq核心设施，用于支持基于NGS的方法；Malgorzata Wygrecka，Kerstin Richter，Alessandro Ianni，Sylvain Maenner和Bruno Charpentier用于试剂；多米尼克·杜马斯支持共聚焦显微镜；Amine Armich、Jean Baptiste Vincourt、Sylvie Fournel Gigleux、Mohamed Ouzzine、Sandrine Gulberti、Catherine Bui、Lydia Barré和Nick Ramalanjaona发表评论。

GB was funded by the “Centre National de la Recherche Scientifique” (CNRS, France), “Délégation Centre-Est” (CNRS-DR6) and the “Lorraine Université” (LU, France) through the initiative “Lorraine Université d’Excellence” (LUE) and the dispositive “Future Leader”, the Max-Planck-Society (MPG, Munich, Germany) and the “Deutsche Forschungsgemeinschaft” (DFG, Bonn, Germany) (BA 4036/4-1).

GB由“国家科学研究中心”（法国国家科学研究中心）、“国家科学研究中心”（法国国家科学研究中心-DR6）和“洛林大学”（法国LU）通过“洛林卓越大学”（LUE）和果断的“未来领袖”、马克斯·普朗克学会（MPG，德国慕尼黑）和“德国科学基金会”（DFG，德国波恩）（BA 4036/4-1）资助。

G.D. and J.C. are supported by the CRC 1366 (Projects A03, A06), the CRC 873 (Project A16), the CRC1550 (Project A03) funded by the DFG, the DZHK (81Z0500202) funded by BMBF, the Medical Faculty Mannheim of University of Heidelberg (90703207) and the Baden‐Württemberg foundation special program “Angioformatics single cell platform”.

G、 D.和J.C.得到了由DFG资助的CRC 1366（项目A03，A06），CRC 873（项目A16），CRC1550（项目A03），由BMBF资助的DZHK（81Z0500202），海德堡大学曼海姆医学院（90703207）和巴登-符腾堡基金会特别计划“血管形成学单细胞平台”的支持。

G.S. receives a doctoral fellowship through the initiative “Lorraine Université d’Excellence” (LUE). DGRA receives a doctoral fellowship from the DAAD (57552340). K.R. was funded by the “Consejo de Ciencia y Tecnología del Estado de Puebla” (CONCYTEP, Puebla, Mexico) through the initiative International Laboratory EPIGEN.

G、美国通过“洛林卓越大学”（LUE）获得博士研究金。DGRA获得DAAD的博士研究金（57552340）。K、 R.由“普埃布拉科学与技术委员会”（CONCYTEP，普埃布拉，墨西哥）通过国际实验室EPIGEN倡议资助。

T.B. is supported by the Deutsche Forschungsgemeinschaft, Excellence Cluster Cardio-Pulmonary Institute (CPI), Transregional Collaborative Research Center TRR81, TP A02, SFB1213 TP B02, TRR 267 TP A05 and the Germa.

T、 B.由德国科学基金会、卓越集群心肺研究所（CPI）、跨区域合作研究中心TRR81、TP A02、SFB1213 TP B02、TRR 267 TP A05和德国支持。

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PubMed Google ScholarContributionsJ.C., G.S., D.G.R.A., K.R,. A.E., S.M., W.S., J.G., S.G., and G.B. designed and performed the experiments; T.B. and G.D. were involved in study design; G.B. and J.C. designed the study; J.C., G.B., G.S., D.G.R.A., K.R., S.G., W.S., and J.G. analyzed the data; G.B., J.C., G.S., and D.G.R.A.

PubMed谷歌学术贡献。C、，G.S.，D.G.R.A.，K.R，。A、 E.，S.M.，W.S.，J.G.，S.G。和G.B.设计并进行了实验；T、 B.和G.D.参与了研究设计；G、 B.和J.C.设计了这项研究；J、 C.，G.B.，G.S.，D.G.R.A.，K.R.，S.G.，W.S。和J.G.分析了数据；G、 B.，J.C.，G.S。和D.G.R.A。

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Reprints and permissionsAbout this articleCite this articleCordero, J., Swaminathan, G., Rogel-Ayala, D.G. et al. Nuclear microRNA 9 mediates G-quadruplex formation and 3D genome organization during TGF-β-induced transcription.

转载和许可本文引用本文Cordero，J.，Swaminathan，G.，Rogel Ayala，D.G。等人。核microRNA 9在TGF-β诱导的转录过程中介导G-四链体形成和3D基因组组织。

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