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

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Item Type:Article
Title:Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells
Creators Name:Soucie, E.L. and Weng, Z. and Geirsdóttir, L. and Molawi, K. and Maurizio, J. and Fenouil, R. and Mossadegh-Keller, N. and Gimenez, G. and VanHille, L. and Beniazza, M. and Favret, J. and Berruyer, C. and Perrin, P. and Hacohen, N. and Andrau, J.C. and Ferrier, P. and Dubreuil, P. and Sidow, A. and Sieweke, M.H.
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 controlling 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.
Keywords:Cell Differentiation, Cell Lineage, Cell Proliferation, Cultured Cells, Down-Regulation, Embryonic Stem Cells, Genetic Enhancer Elements, Gene Expression Regulation, Gene Regulatory Networks, Macrophages, MafB Transcription Factor, Proto-Oncogene Proteins c-maf, Single-Cell Analysis, Transcriptional Activation, Animals, Mice
Publisher:American Association for the Advancement of Science
Page Range:aad5510
Date:12 February 2016
Official Publication:https://doi.org/10.1126/science.aad5510
PubMed:View item in PubMed

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