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Transcription factor-driven coordination of cell cycle exit and lineage-specification in vivo during granulocytic differentiation

ABSTRACT: Transcription factor-driven coordination of cell cycle exit and lineage-specification in vivo during granulocytic differentiation

PROVIDER: PRJNA668912 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12817020_1.fastq.gz	Fastqsanger.gz
	SRR12817020_2.fastq.gz	Fastqsanger.gz
	SRR12817021_1.fastq.gz	Fastqsanger.gz
	SRR12817021_2.fastq.gz	Fastqsanger.gz
	SRR12817022_1.fastq.gz	Fastqsanger.gz

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Transcription factor-driven coordination of cell cycle exit and lineage-specification in vivo during granulocytic differentiation [ChIP-Seq_2]

Project description: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.

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Transcription factor-driven coordination of cell cycle exit and specification of cell identify during granulocytic differentiation [RNA-Seq]

Project description:Differentiation of multipotent stem cells into mature cells is fundamental for development and homeostasis of mammalian tissues. However, how this temporal process of cell cycle exit and induction of lineage-specific transcription programs is coordinated remains largely unknown. To understand the underlying mechanisms, we investigated how the tissue-specific transcription factors CEBPA and CEBPE coordinate cell cycle exit and lineage-specification during granulocytic differentiation. We demonstrate that CEBPA promotes lineage-commitment 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 terminal differentiation through the use of distinct gene regulatory elements.

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Transcription factor-driven coordination of cell cycle exit and lineage-specification in vivo during granulocytic differentiation [ChIP-Seq_2]

Project description:Transcription factor-driven coordination of cell cycle exit and lineage-specification in vivo during granulocytic differentiation [ChIP-Seq_2]

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Transcription factor-driven coordination of cell cycle exit and specification of cell identify during granulocytic differentiation [ChIP-Seq]

Project description:Transcription factor-driven coordination of cell cycle exit and specification of cell identify during granulocytic differentiation [ChIP-Seq]

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Transcription factor-driven coordination of cell cycle exit and specification of cell identify during granulocytic differentiation [RNA-Seq]

Project description:Transcription factor-driven coordination of cell cycle exit and specification of cell identify during granulocytic differentiation [RNA-Seq]

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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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Transcription factor-driven coordination of cell cycle exit and lineage-specification in vivo during granulocytic differentiation

Project description:This SuperSeries is composed of the SubSeries listed below.

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Foxd3 promotes the exit from naïve pluripotency and prevents germline specification through enhancer decommissioning [ChIP-Seq]

Project description:Following implantation, mouse epiblast cells transit from a naïve to a primed state in which they are competent for both somatic and primordial germ cell (PGC) specification. Using mouse embryonic stem cells (mESC) as an in vitro model to study the transcriptional regulatory principles orchestrating peri-implantation development, here we show that the transcription factor Foxd3 is necessary for the exit from naïve pluripotency and the progression to a primed pluripotent state. During this transition, Foxd3 acts as a repressor that dismantles a significant fraction of the naïve pluripotency expression program through the decommissioning of active enhancers associated with key naïve pluripotency and early germline genes. Subsequently, Foxd3 needs to be silenced in primed pluripotent cells to allow the reactivation of relevant genes required for proper PGC specification. Our findings uncover a wave of activation-deactivation of Foxd3 as a crucial step for the exit from naïve pluripotency and subsequent PGC specification. Genome-wide binding profiles for Foxd3 were investigated in mouse embryonic stem cells (mESC). A mESC line (FH-Foxd3 mESC line) expressing exogenous Foxd3 tagged with Flag and HA epitope (FH-Foxd3) at nearly endogenous levels was generated. ChIPs were performed against FH-Foxd3 using anti-HA or anti-Flag antibodies.

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Foxd3 promotes the exit from naïve pluripotency and prevents germline specification through enhancer decommissioning [RNA-Seq]

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