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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Transcription factor-driven coordination of cell cycle exit and lineage-specification in vivo during granulocytic differentiation : In memoriam Professor Niels Borregaard. / Theilgaard-Mönch, Kim; Pundhir, Sachin; Reckzeh, Kristian; Su, Jinyu; Tapia, Marta; Furtwängler, Benjamin; Jendholm, Johan; Jakobsen, Janus Schou; Hasemann, Marie Sigurd; Knudsen, Kasper Jermiin; Cowland, Jack Bernard; Fossum, Anna; Schoof, Erwin; Schuster, Mikkel Bruhn; Porse, Bo T.
In: Nature Communications, Vol. 13, No. 1, 3595, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Transcription factor-driven coordination of cell cycle exit and lineage-specification in vivo during granulocytic differentiation
T2 - In memoriam Professor Niels Borregaard
AU - Theilgaard-Mönch, Kim
AU - Pundhir, Sachin
AU - Reckzeh, Kristian
AU - Su, Jinyu
AU - Tapia, Marta
AU - Furtwängler, Benjamin
AU - Jendholm, Johan
AU - Jakobsen, Janus Schou
AU - Hasemann, Marie Sigurd
AU - Knudsen, Kasper Jermiin
AU - Cowland, Jack Bernard
AU - Fossum, Anna
AU - Schoof, Erwin
AU - Schuster, Mikkel Bruhn
AU - Porse, Bo T
N1 - © 2022. The Author(s).
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-022-31332-1
DO - 10.1038/s41467-022-31332-1
M3 - Journal article
C2 - 35739121
VL - 13
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 3595
ER -
ID: 311509515