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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., 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, J.C., Ferrier, P., Dubreuil, P., 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
Source:Science
ISSN:0036-8075
Publisher:American Association for the Advancement of Science
Volume:351
Number:6274
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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