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Rigshospitalet - en del af Københavns Universitetshospital
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Transcription factor-driven coordination of cell cycle exit and lineage-specification in vivo during granulocytic differentiation: In memoriam Professor Niels Borregaard

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DOI

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Vis graf over relationer

Differentiation of multipotent stem cells into mature cells is fundamental for development and homeostasis of mammalian tissues, and requires the coordinated induction of lineage-specific transcriptional programs and cell cycle withdrawal. To understand the underlying regulatory mechanisms of this fundamental process, we investigated how the tissue-specific transcription factors, CEBPA and CEBPE, coordinate cell cycle exit and lineage-specification in vivo during granulocytic differentiation. We demonstrate that CEBPA promotes lineage-specification by launching an enhancer-primed differentiation program and direct activation of CEBPE expression. Subsequently, CEBPE confers promoter-driven cell cycle exit by sequential repression of MYC target gene expression at the G1/S transition and E2F-meditated G2/M gene expression, as well as by the up-regulation of Cdk1/2/4 inhibitors. Following cell cycle exit, CEBPE unleashes the CEBPA-primed differentiation program to generate mature granulocytes. These findings highlight how tissue-specific transcription factors coordinate cell cycle exit with differentiation through the use of distinct gene regulatory elements.

OriginalsprogEngelsk
TidsskriftNature Communications
Vol/bind13
Udgave nummer1
Sider (fra-til)3595
ISSN2041-1722
DOI
StatusUdgivet - 23 jun. 2022

Bibliografisk note

© 2022. The Author(s).

ID: 79002645