MassIVE MSV000095480

Partial Public PXD054375

3D genome organization during TGFB-induced transcription requires nuclear microRNA and G-quadruplexes

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Description

Studying the dynamics of three-dimensional (3D) chromatin structure is essential to the understanding of biological processes in the nucleus. Integrative analysis of multi-omics data in recent publications have provided comprehensive and multilevel insight into 3D genome organization emphasizing its role for transcriptional regulation. While enhancers are regulatory elements that play a central role in the spatiotemporal control of gene expression, chromatin looping has been broadly accepted as a means for enhancer-promoter interactions yieldingcell-type-specific gene expression signatures. On the other hand, G-quadruplexes (G4s) are non-canonical DNA secondary structures that are enriched at promoters and related to increased gene expression, both. A role for G4s in promoter-distal regulatory elements, such as super-enhancers (SE), as well as in 3D genome organization and chromatin looping mediating long-range enhancer-promoter interactions has, however, remained elusive. Here we show that mature microRNA 9 (miR-9) is enriched at promoters and SE of genes that are inducible by tissue growth factor beta 1 (TGFB1) signaling. Further, we find that nuclear miR-9 is required for chromatin features related to increased transcriptional activity, such as broad domains of the euchromatin histone mark H3K4me3 (histone 3 tri-methylated lysine 4) and G4s. Moreover, we show that nuclear miR-9 is required for promoter-super-enhancer looping. Our study places a nuclear microRNA in the same structural and functional context with G4s and promoter-enhancer interactions during 3D genome organization and transcriptional activation induced by TGFB1 signaling, a critical regulator of proliferation programs in cancer and fibrosis. [doi:10.25345/C5639KH31] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: TimsTof, sp3, mouse, interactome

Contact

Principal Investigators:
(in alphabetical order) 		Guillermo Barreto, Universite de Lorraine, CNRS, Laboratoire IMoPA, Nancy, France
Submitting User: Wszymanski

Publications

Cordero J, Swaminathan G, Rogel-Ayala DG, Rubio K, Elsherbiny A, Mahmood S, Szymanski W, Graumann J, Braun T, Günther S, Dobreva G, Barreto G.
Nuclear microRNA 9 mediates G-quadruplex formation and 3D genome organization during TGF-?-induced transcription.
Nat Commun. 2024 Dec 20;15(1):10711. Epub 2024 Dec 20.

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