Lineage-specific Enhancers Activate Self-renewal Genes in Macrophages and Embryonic Stem Cells

Overview

Journal Science

Specialty Science

Date 2016 Jan 23

PMID 26797145

Citations 127

Authors

Erinn L Soucie

Ziming Weng

Laufey Geirsdottir

Kaaweh Molawi

Julien Maurizio

Romain Fenouil

Noushine Mossadegh-Keller

Gregory Gimenez

Laurent Vanhille

Meryam Beniazza

Jeremy Favret

Carole Berruyer

Pierre Perrin

Nir Hacohen

J-C Andrau

Pierre Ferrier

Patrice Dubreuil

Arend Sidow

Michael H Sieweke

Affiliations

Soon will be listed here.

Abstract

Differentiated macrophages can self-renew in tissues and expand long term in culture, but the gene regulatory mechanisms that accomplish self-renewal in the differentiated state have remained unknown. Here we show that in mice, the transcription factors MafB and c-Maf repress a macrophage-specific enhancer repertoire associated with a gene network that controls self-renewal. Single-cell analysis revealed that, in vivo, proliferating resident macrophages can access this network by transient down-regulation of Maf transcription factors. The network also controls embryonic stem cell self-renewal but is associated with distinct embryonic stem cell-specific enhancers. This indicates that distinct lineage-specific enhancer platforms regulate a shared network of genes that control self-renewal potential in both stem and mature cells.

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