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

IF 14.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Julio Cordero, Guruprasadh Swaminathan, Diana G. Rogel-Ayala, Karla Rubio, Adel Elsherbiny, Samina Mahmood, Witold Szymanski, Johannes Graumann, Thomas Braun, Stefan Günther, Gergana Dobreva, Guillermo Barreto
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引用次数: 0

Abstract

The 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. 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. 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.

Abstract Image

在TGF-β诱导的转录过程中,核microRNA 9介导g -四重体形成和3D基因组组织
三维(3D)基因组的动态组织对转录调控至关重要。增强子调控时空基因表达,染色质循环是增强子-启动子相互作用的一种手段,可产生细胞类型特异性基因表达。此外,非规范 DNA 二级结构(如 G-四重链(G4s))与基因表达的增加有关。然而,G4s 在启动子-远端调控元件(如超级增强子 (SE))和染色质环路中的作用仍然难以捉摸。在这里,我们发现成熟的 microRNA 9(miR-9)富集在可被转化生长因子 beta1(TGFB1)信号诱导的基因的启动子和 SE 中。此外,我们还发现 miR-9 是在 TGFB1 反应基因上形成 G4s、启动子-超级增强子循环和外染色质组蛋白标记 H3K4me3 宽域所必需的。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,即在三维基因组组织和TGFB1信号(癌症和纤维化的关键信号通路)诱导的转录激活过程中。
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来源期刊
Nature Communications
Nature Communications Biological Science Disciplines-
CiteScore
24.90
自引率
2.40%
发文量
6928
审稿时长
3.7 months
期刊介绍: Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.
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