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

Author(s):Show less -

Cuartero, Sergi ^[1] ; Weiss, Felix D. ^[1] ; Dharmalingam, Gopuraja ^[2] ; Guo, Ya ^[1] ; Ing-Simmons, Elizabeth ^{[3, 1, 4]} ; Masella, Silvia ^[5] ; Robles-Rebollo, Irene ^[1] ; Xiao, Xiaolin ^[2] ; Wang, Yi-Fang ^[2] ; Barozzi, Iros ^{[5, 6]} ; Djeghloul, Dounia ^[1] ; Amano, Mariane T. ^{[7, 1]} ; Niskanen, Henri ^[8] ; Petretto, Enrico ^{[2, 9]} ; Dowell, Robin D. ^{[10, 11]} ; Tachibana, Kikue ^{[12, 13]} ; Kaikkonen, Minna U. ^[8] ; Nasmyth, Kim A. ^[12] ; Lenhard, Boris ^[3] ; Natoli, Gioacchino ^{[14, 15]} ; Fisher, Amanda G. ^[1] ; Merkenschlager, Matthias ^[1]

Affiliation:Show less -

^[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, Inst Clin Sci, Fac Med, London - England

^[3] Imperial Coll London, MRC London Inst Med Sci, Computat Regulatory Genom Grp, Integrat Biol Sect, Inst Clin Sci, Fac Med, London - England

^[4] Max Planck Inst Mol Biomed, Munster - Germany

^[5] European Inst Oncol, Dept Expt Oncol, Milan - Italy

^[6] Imperial Coll London, Dept Surg & Canc, Dept Med, London - England

^[7] Hosp Sirio Libanes, Sao Paulo - Brazil

^[8] Univ Eastern Finland, AI Virtanen Inst Mol Sci, Kuopio - Finland

^[9] Duke NUS Med Sch, Cardiovasc & Metab Disorders, Singapore - Singapore

^[10] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 - USA

^[11] Univ Colorado, BioFrontiers Inst, Boulder, CO 80309 - USA

^[12] Univ Oxford, Dept Biochem, Oxford - England

^[13] Austrian Acad Sci, Vienna Bioctr, Inst Mol Biotechnol, Vienna - Austria

^[14] Humanitas Clin & Res Ctr, Milan - Italy

^[15] Humanitas Univ, Milan - Italy

• Document type: Journal article
• Source: NATURE IMMUNOLOGY; v. 19, n. 9, p. 932+, SEP 2018.
• Web of Science Citations: 21

Abstract

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. (AU)

• FAPESP's process: 14/20861-3 - The role of cohesin mutations in myeloid malignancies development
• Grantee: Mariane Tami Amano
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor