Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells

Erinn L. Soucie*, Ziming Weng, Laufey Geirsdóttir, 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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numberaad5510
JournalScience
Volume351
Issue number6274
DOIs
Publication statusPublished - 12 Feb 2016

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