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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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.
Original language | English |
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Article number | 3595 |
Journal | Nature Communications |
Volume | 13 |
Issue number | 1 |
Number of pages | 17 |
ISSN | 2041-1723 |
DOIs | |
Publication status | Published - 2022 |
Bibliographical note
© 2022. The Author(s).
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