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FBXL19 recruits CDK8-Mediator to CpG islands and primes developmental genes for activation during lineage commitment

ABSTRACT: FBXL19 recruits CDK8-Mediator to CpG islands and primes developmental genes for activation during lineage commitment

PROVIDER: PRJNA386109 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5520690_1.fastq.gz	Fastqsanger.gz
	SRR5520690_2.fastq.gz	Fastqsanger.gz
	SRR5520730.fastq.gz	Fastqsanger.gz
	SRR5520740_1.fastq.gz	Fastqsanger.gz
	SRR5520740_2.fastq.gz	Fastqsanger.gz

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FBXL19 transcriptionally primes promoters of developmental genes via CDK8-Mediator recruitment [RNA-seq]

Project description:Regulatory elements called CpG islands (CGIs) are associated with the majority of mammalian gene promoters and have been proposed to play an important role in gene expression. The regulatory capacity of CGIs is thought to rely upon a family of proteins that recognise CGIs through their ZF-CxxC DNA binding domains to recruit chromatin-modifying activities to gene promoters. Through studying FBXL19, a poorly characterized ZF-CxxC domain-containing protein, we have discovered that it specifically interacts with the CDK8-Mediator complex in mouse embryonic stem cells (ESCs). Intriguingly, FBXl19 recruits CDK8-Mediator to a subset of CGI-associated promoters of repressed developmental genes in ESCs. We show that FBXL19-dependent recruitment of CDK8 in ESCs is required for the proper induction of the associated genes during ESC differentiation. This is consistent with early embryonic lethality of in FBXl19 deficient mice. Together, our observations highlight a novel role for FBXL19 in priming developmental gene expression, via recruitment of CDK8 to their CGI promoters, in order to support normal gene induction during differentiation and development.

2018-06-08 | GSE98755 | GEO

FBXL19 transcriptionally primes promoters of developmental genes via CDK8-Mediator recruitment [ChIP-seq 2]

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FBXL19 transcriptionally primes promoters of developmental genes via CDK8-Mediator recruitment [ChIP-seq 1]

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Fbxl19 recruits Rnf20 to CpG Islands and promotes H2B mono-ubiquitination [Affymetrix]

Project description:Rnf20 catalyzes lysine 120 mono-ubiquitination of histone H2B (H2Bub1) that has been previously involved in normal differentiation of embryonic stem (ES) and adult stem cells. However, the mechanisms underlying by which Rnf20 is recruited to its target chromosomal loci to generate H2Bub1 are still elusive. Here, we reveal that Fbxl19, a CxxC domain-containing protein, physically interacts with Rnf20, guides it preferentially to CpG island-containing target promoters, and thereby promotes mono-ubiqutination of H2B. We first show that up-regulation of Fbxl19 induces the level of global H2Bub1, while down-regulation of Fbxl19 reduces the level of H2Bub1 in mouse ES cells. Our genome-wide target mapping unveils the preferential occupancy of Fbxl19 on CpG island-containing promoters, and we further show that the binding of Fbxl19 is essential for the recruitment of Rnf20 to its target genes and subsequent H2Bub1. Altogether, our results demonstrate that Fbxl19 plays critical roles in the H2Bub1 pathway by recruiting Rnf20 to CGI target genes specifically and selectively.

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FBXL19 recruits CDK8-Mediator to CpG islands and primes developmental genes for activation during lineage commitment

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

2018-06-08 | GSE98756 | GEO

Fbxl19 recruits Rnf20 to CpG Islands and promotes H2B mono-ubiquitination [ChIP-Seq]

Project description:Rnf20 catalyzes lysine 120 mono-ubiquitination of histone H2B (H2Bub1) that has been previously invloved in normal differentiation of embryonic stem (ES) and adult stem cells. However,the mechanims underlying by which Rnf20 is recruited to its target chromosomal loci to generate H2Bub1 is still elusive. Here, we reveal that Fbxl19, a CxxC domain-containing protein, physically interacts with Rnf20, guides it preferentially to CpG island-containing target promoters, and thereby promotes mono-ubiqutination of H2B. We first show that up-regulation of Fbxl19 induces the level of global H2Bub1, while down-regulation of Fbxl19 reduces the level of H2Bub1 in mouse ES cells. Our genome-wide target mapping unveils the preferential occupancy of Fbxl19 on CpG island-containing promoters, and we further show that the binding of Fbxl19 is essential for the recruitment of Rnf20 to its target genes and subsequent H2Bub1. Altogether, our results demonstrate that Fbxl19 plays critical roles in the H2Bub1 pathway by recruiting Rnf20 to CGI target genes specifically and selectively.

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Fbxl19 recruits Rnf20 to CpG Islands and promotes H2B mono-ubiquitination

Project description:Fbxl19 recruits Rnf20 to CpG Islands and promotes H2B mono-ubiquitination

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FBXL19 recruits CDK-Mediator to CpG islands of developmental genes priming them for activation during lineage commitment.

Project description:CpG islands are gene regulatory elements associated with the majority of mammalian promoters, yet how they regulate gene expression remains poorly understood. Here, we identify FBXL19 as a CpG island-binding protein in mouse embryonic stem (ES) cells and show that it associates with the CDK-Mediator complex. We discover that FBXL19 recruits CDK-Mediator to CpG island-associated promoters of non-transcribed developmental genes to prime these genes for activation during cell lineage commitment. We further show that recognition of CpG islands by FBXL19 is essential for mouse development. Together this reveals a new CpG island-centric mechanism for CDK-Mediator recruitment to developmental gene promoters in ES cells and a requirement for CDK-Mediator in priming these developmental genes for activation during cell lineage commitment.

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Fbxl19 recruits Rnf20 to CpG Islands and promotes H2B mono-ubiquitination

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

2016-10-01 | GSE76570 | GEO

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Project description:FBXL19 transcriptionally primes promoters of developmental genes via CDK8-Mediator recruitment [RNA-seq]

| PRJNA386118 | ENA