期刊
JOURNAL OF CELL SCIENCE
卷 130, 期 9, 页码 1570-1582出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.199216
关键词
Heterochromatin; Histone variant; Nuclear organization; DNA repeats
类别
资金
- Ministerio de Economia y Competitividad (MINECO) [BFU2015-66559-P, BES-2010-031876, JCI-2011-10831]
- Jose Carreras Leukamie-Stiftung [DJCLS R 14/16]
- AFM-Telethon [AFM 18738]
- Marie Sklodowska-Curie Actions Training network [H2020-MSCA-ITN-2015-675610]
- Agencia de Gestio d'Ajuts Universitaris i de Recerca [2014-SGR-35]
- Ministerio de Educacion, Cultura y Deporte (MECD)-FPU [FPU14/06542]
- Marie Curie Fellowship [INTEGER 214902]
- European Network of Excellence [EpiGeneSys 257082]
- European Commission
- la Caixa Foundation
- Fundacio Internacional Josep Carreras, Celgene, Spain
- Centres de Recerca de Catalunya, Generalitat de Catalunya
Genetic loss-of-function studies on development, cancer and somatic cell reprogramming have suggested that the group of macroH2A histone variants might function through stabilizing the differentiated state by a yet unknown mechanism. Here, we present results demonstrating that macroH2A variants have a major function in maintaining nuclear organization and heterochromatin architecture. Specifically, we find that a substantial amount of macroH2A is associated with heterochromatic repeat sequences. We further identify macroH2A on sites of interstitial heterochromatin decorated by histone H3 trimethylated on K9 (H3K9me3). Loss of macroH2A leads to major defects in nuclear organization, including reduced nuclear circularity, disruption of nucleoli and a global loss of dense heterochromatin. Domains formed by DNA repeat sequences are disorganized, expanded and fragmented, and mildly re-expressed when depleted of macroH2A. At the molecular level, we find that macroH2A is required for the interaction of repeat sequences with the nucleostructural protein lamin B1. Taken together, our results argue that a major function of macroH2A histone variants is to link nucleosome composition to higher-order chromatin architecture.
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