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

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...

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Veröffentlicht in:	Nature immunology Jg. 19; H. 9; S. 932 - 941
Hauptverfasser:	Cuartero, Sergi, Weiss, Felix D., Dharmalingam, Gopuraja, Guo, Ya, Ing-Simmons, Elizabeth, Masella, Silvia, Robles-Rebollo, Irene, Xiao, Xiaolin, Wang, Yi-Fang, Barozzi, Iros, Djeghloul, Dounia, Amano, Mariane T., Niskanen, Henri, Petretto, Enrico, Dowell, Robin D., Tachibana, Kikuë, Kaikkonen, Minna U., Nasmyth, Kim A., Lenhard, Boris, Natoli, Gioacchino, Fisher, Amanda G., Merkenschlager, Matthias
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	New York Nature Publishing Group US 01.09.2018 Nature Publishing Group
Schlagworte:	631/250/2504/342 631/337/100 631/67/1990 Acute myeloid leukemia Animals Biomedical and Life Sciences Biomedicine Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Cell Differentiation - genetics Cell Self Renewal - genetics Cell self-renewal Cells, Cultured Chromosomal Proteins, Non-Histone - genetics Chromosomal Proteins, Non-Histone - metabolism Cohesin Cohesins DNA-Binding Proteins Gene expression Gene Expression Regulation Genomes Hematopoietic stem cells Hematopoietic Stem Cells - physiology High-Throughput Nucleotide Sequencing Humans Immunology Infectious Diseases Inflammation Inflammation - genetics Leukemia Leukemia, Myeloid, Acute - genetics Lipopolysaccharides - immunology Macrophages Macrophages - physiology Mice Mice, Knockout Mutation Mutation - genetics Myeloid leukemia Nuclear Proteins - genetics Phosphoproteins - genetics Progenitor cells Transcription
ISSN:	1529-2908, 1529-2916, 1529-2916
Online-Zugang:	Volltext
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Zusammenfassung:	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. Cohesin is a chromatin-binding factor that interacts at CTCF motifs to organize chromatin looping domains. Merkenschlager and colleagues show that cohesin regulates the inducible expression of inflammatory genes in macrophages and HSPCs and in human AML.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Present addresses: Max Planck Institute for Molecular Biomedicine, Muenster, Germany (LIS), Hospital Sírio-Libanês, Sao Paulo, Brazil (MTA), Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna Biocenter, Vienna, Austria (KT)
ISSN:	1529-2908 1529-2916 1529-2916
DOI:	10.1038/s41590-018-0184-1