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

Publié dans: Science, 2016, 351 (6274), pp.680-U123. ⟨10.1126/science.aad5510⟩

Auteurs: Erinn L. Soucie, Ziming Weng, Laufey Geirsdottir, Kaaweh Molawi, Julien Maurizio, Romain Fenouil, Noushine Mossadegh, 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

Résumé

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.

Lien vers Pubmed [PMID] – 26797145

Lien vers HAL – hal-01438535

Lien vers le DOI – 10.1126/science.aad5510