The histone variant macroH2A1.1 regulates RNA polymerase II-paused genes within defined chromatin interaction landscapes

被引：8

作者：

Recoules, Ludmila ^{[1
,2
]}

Heurteau, Alexandre ^{[1
,2
]}

Raynal, Flavien ^{[1
,2
]}

Karasu, Nezih ^{[3
,4
]}

Moutahir, Fatima ^{[1
,2
]}

Bejjani, Fabienne ^{[5
,6
]}

Jariel-Encontre, Isabelle ^{[5
,6
]}

Cuvier, Olivier ^{[1
,2
]}

Sexton, Thomas ^{[3
,4
]}

Lavigne, Anne-Claire ^{[1
,2
]}

Bystricky, Kerstin ^{[1
,2
,7
]}

机构：

[1] Univ Toulouse, Mol Cellular & Dev Biol MCD, UMR5077, Ctr Biol Integrat CBI,CNRS,UPS, F-31062 Toulouse, France

[2] UPS, CNRS, CBI, Chromatin Dynam FRM Team, F-31062 Toulouse, France

[3] Univ Strasbourg, Inst Genet & Biol Mol & Cellulaire IGBMC, CNRS, UMR7104, F-67400 Illkirch Graffenstaden, France

[4] Univ Strasbourg, INSERM U1258, F-67400 Illkirch Graffenstaden, France

[5] CNRS, UMR5535, Inst Genet Mol Montpellier IGMM, F-34293 Montpellier, France

[6] Equipe Labellisee Ligue Natl Canc, F-34293 Montpellier, France

[7] Inst Univ France IUF, 1 Rue Descartes, F-75231 Paris, France

来源：

JOURNAL OF CELL SCIENCE | 2022年 / 135卷 / 07期

基金：

欧洲研究理事会; 欧盟地平线“2020”;

关键词：

Histone variants; RNA polymerase II-paused genes; Gene expression; Chromatin structure; Cellular migration; Breast cancer; R/BIOCONDUCTOR PACKAGE; TRANSCRIPTION FACTORS; EPIGENETIC REGULATOR; ENHANCERS; ROLES; ISOFORMS; BINDING; PROGRESSION; INTERFERES; ACTIVATION;

D O I：

10.1242/jcs.259456

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The histone variant macroH2A1.1 plays a role in cancer development and metastasis. To determine the underlying molecular mechanisms, we mapped the genome-wide localization of endogenous macroH2A1.1 in the human breast cancer cell line MDA-MB-231. We demonstrate that macroH2A1.1 specifically binds to active promoters and enhancers in addition to facultative heterochromatin. Selective knock down of macroH2A1.1 deregulates the expression of hundreds of highly active genes. Depending on the chromatin landscape, macroH2A1.1 acts through two distinct molecular mechanisms. The first mitigates excessive transcription by binding over domains including the promoter and the gene body. The second stimulates expression of RNA polymerase II (Pol II)-paused genes, including genes regulating mammary tumor cell migration. In contrast to the first mechanism, macroH2A1.1 specifically associates with the transcription start site of Pol II-paused genes. These processes occur in a predefined local 3D genome landscape, but do not require rewiring of enhancer-promoter contacts. We thus propose that macroH2A1.1 serves as a transcriptional modulator with a potential role in assisting the conversion of promoter-locked Pol II into a productive, elongating Pol II.

引用

页数：17