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.

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

Natoli, Gioacchino;
2018

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.
Animals
Cell Cycle Proteins
Cell Differentiation
Cell Self Renewal
Cells, Cultured
Chromosomal Proteins, Non-Histone
DNA-Binding Proteins
Gene Expression Regulation
Hematopoietic Stem Cells
High-Throughput Nucleotide Sequencing
Humans
Inflammation
Leukemia, Myeloid, Acute
Lipopolysaccharides
Macrophages
Mice
Mice, Knockout
Mutation
Nuclear Proteins
Phosphoproteins
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11699/59345
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