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Feb 2016 Science (New York, N.Y.)

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


Soucie EL, Weng Z, Geirsdóttir L, Molawi K, Maurizio J, Fenouil R, Mossadegh-Keller N, Gimenez G, VanHille L, Beniazza M, Favret J, Berruyer C, Perrin P, Hacohen N, Andrau JC, Ferrier P, Dubreuil P, Sidow A, Sieweke MH


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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