Control of inducible gene expression links cohesin to hematopoietic progenitor self-renewal and differentiation

被引：156

作者：

Cuartero, Sergi ^{[1
]}

Weiss, Felix D. ^{[1
]}

Dharmalingam, Gopuraja ^{[3
]}

Guo, Ya ^{[1
]}

Ing-Simmons, Elizabeth ^{[1
,2
,13
]}

Masella, Silvia ^{[4
]}

Robles-Rebollo, Irene ^{[1
]}

Xiao, Xiaolin ^{[3
]}

Wang, Yi-Fang ^{[3
]}

Barozzi, Iros ^{[4
,5
]}

Djeghloul, Dounia ^{[1
]}

Amano, Mariane T. ^{[1
,14
]}

Niskanen, Henri ^{[6
]}

Petretto, Enrico ^{[3
,7
]}

Dowell, Robin D. ^{[8
,9
]}

Tachibana, Kikue ^{[10
,15
]}

Kaikkonen, Minna U. ^{[6
]}

Nasmyth, Kim A. ^{[10
]}

Lenhard, Boris ^{[2
]}

Natoli, Gioacchino ^{[11
,12
]}

Fisher, Amanda G. ^{[1
]}

Merkenschlager, Matthias ^{[1
]}

机构：

[1] Imperial Coll London, MRC London Inst Med Sci, Inst Clin Sci, Epigenet Sect,Lymphocyte Dev Grp,Fac Med, London, England

[2] Imperial Coll London, MRC London Inst Med Sci, Computat Regulatory Genom Grp, Integrat Biol Sect,Inst Clin Sci,Fac Med, London, England

[3] Imperial Coll London, MRC London Inst Med Sci, Inst Clin Sci, Fac Med, London, England

[4] European Inst Oncol, Dept Expt Oncol, Milan, Italy

[5] Imperial Coll London, Dept Surg & Canc, Dept Med, London, England

[6] Univ Eastern Finland, AI Virtanen Inst Mol Sci, Kuopio, Finland

[7] Duke NUS Med Sch, Cardiovasc & Metab Disorders, Singapore, Singapore

[8] Univ Colorado, BioFrontiers Inst, Boulder, CO 80309 USA

[9] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA

[10] Univ Oxford, Dept Biochem, Oxford, England

[11] Humanitas Clin & Res Ctr, Milan, Italy

[12] Humanitas Univ, Milan, Italy

[13] Max Planck Inst Mol Biomed, Munster, Germany

[14] Hosp Sirio Libanes, Sao Paulo, Brazil

[15] Austrian Acad Sci, Vienna Bioctr, Inst Mol Biotechnol, Vienna, Austria

来源：

NATURE IMMUNOLOGY | 2018年 / 19卷 / 09期

基金：

英国医学研究理事会; 美国国家科学基金会; 欧洲研究理事会; 芬兰科学院; 英国惠康基金;

关键词：

STEM-CELLS; INSULATED NEIGHBORHOODS; TRANSCRIPTION FACTORS; REVEALS PRINCIPLES; CHROMATIN DOMAINS; GENOME; COMPLEX; ACTIVATION; CTCF; ORGANIZATION;

D O I：

10.1038/s41590-018-0184-1

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Cohesin is important for 3D genome organization. Nevertheless, even the complete removal of cohesin has surprisingly little impact on steady-state gene transcription and enhancer activity. Here we show that cohesin is required for the core transcriptional response of primary macrophages to microbial signals, and for inducible enhancer activity that underpins inflammatory gene expression. Consistent with a role for inflammatory signals in promoting myeloid differentiation of hematopoietic stem and progenitor cells (HPSCs), cohesin mutations in HSPCs led to reduced inflammatory gene expression and increased resistance to differentiation-inducing inflammatory stimuli. These findings uncover an unexpected dependence of inducible gene expression on cohesin, link cohesin with myeloid differentiation, and may help explain the prevalence of cohesin mutations in human acute myeloid leukemia.

引用

页码：932 / +

页数：19

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