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

Erinn L. Soucie (1) , Ziming Weng , Laufey Geirsdottir (1) , Kaaweh Molawi (1) , Julien Maurizio (1) , Romain Fenouil (1) , Noushine Mossadegh (1) , Gregory Gimenez (1) , Laurent Vanhille (1) , Meryam Beniazza (1) , Jeremy Favret (1) , Carole Berruyer (1) , Pierre Perrin (1) , Nir Hacohen , J. -C. Andrau (1) , Pierre Ferrier (1) , Patrice Dubreuil , Arend Sidow , Michael H. Sieweke (1)

1 CIML - Centre d'Immunologie de Marseille - Luminy

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.

Domaines: Immunologie

Erinn L. Soucie, Ziming Weng, Laufey Geirsdottir, Kaaweh Molawi, Julien Maurizio, et al.. Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells. Science, 2016, 351 (6274), pp.680-U123. ⟨10.1126/science.aad5510⟩. ⟨hal-01438535⟩