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

Soucie, E. L.; Weng, Z.; Geirsdottir, 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, J. C.; Ferrier, P.; Dubreuil, P.; Sidow, A.; Sieweke, M. H.


2016-02-12 / vol 351 / pages aad5510


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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1095-9203 (Electronic) 0036-8075 (Linking)

PMCID: PMC4811353


*Gene Expression Regulation; Animals; Cell Differentiation/*genetics; Cell Lineage/*genetics; Cell Proliferation; Cells, Cultured; Down-Regulation; Embryonic Stem Cells/*cytology; Enhancer Elements, Genetic/*physiology; Gene Regulatory Networks; Macrophages/*cytology; MafB Transcription Factor/metabolism; Mice; Proto-Oncogene Proteins c-maf/metabolism; Single-Cell Analysis; Transcriptional Activation

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