Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells.
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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 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. |
Year of Publication | 2016
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Journal | Science
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Volume | 351
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Issue | 6274
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Pages | aad5510
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Date Published | 2016 Feb 12
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ISSN | 1095-9203
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URL | |
DOI | 10.1126/science.aad5510
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PubMed ID | 26797145
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PubMed Central ID | PMC4811353
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Grant list | P01 AG036695 / AG / NIA NIH HHS / United States
P01AG036695 / AG / NIA NIH HHS / United States
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