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Chromatin binding of CFP1 mutants in C127 mouse cell lines. [C127_ChIPseq]

ABSTRACT: Chromatin modifications and the promoter associated epigenome are thought to be important for the regulation of gene expression. However, the mechanisms by which chromatin modifying complexes are targeted to the appropriate gene promoters in vertebrates and how they influence gene expression have remained poorly defined. Here, using a combination of live cell imaging and functional genomics, we discover that the vertebrate SET1 complex is targeted to actively transcribed target gene promoters through CFP1 which engages in a unique form of multivalent chromatin reading that involves recognition of non-methylated DNA and histone H3 lysine 4 trimethylation (H3K4me3). CFP1 defines SET1 complex occupancy on chromatin and its multivalent interactions are required for the SET1 complex to place H3K4me3. In the absence of CFP1, gene expression is perturbed suggesting that the normal targeting and function of SET1 complex is central to creating an appropriately functioning vertebrate promoter associated epigenome.

ORGANISM(S): Mus musculus

PROVIDER: GSE93428 | GEO | 2017/09/05

SECONDARY ACCESSION(S): PRJNA361189

REPOSITORIES: GEO

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CFP1/SET1 complex occupancy and H3K4me3 profile in CFP1 fl/fl ES cells and rescue lines. [mESC_ChIPseq]

Project description:Chromatin modifications and the promoter associated epigenome are thought to be important for the regulation of gene expression. However, the mechanisms by which chromatin modifying complexes are targeted to the appropriate gene promoters in vertebrates and how they influence gene expression have remained poorly defined. Here, using a combination of live cell imaging and functional genomics, we discover that the vertebrate SET1 complex is targeted to actively transcribed target gene promoters through CFP1 which engages in a unique form of multivalent chromatin reading that involves recognition of non-methylated DNA and histone H3 lysine 4 trimethylation (H3K4me3). CFP1 defines SET1 complex occupancy on chromatin and its multivalent interactions are required for the SET1 complex to place H3K4me3. In the absence of CFP1, gene expression is perturbed suggesting that the normal targeting and function of SET1 complex is central to creating an appropriately functioning vertebrate promoter associated epigenome.

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Cfp1 is required for gene expression dependent H3K4me3 and H3K9 acetylation in embryonic stem cells (ChIP-Seq)

Project description:Trimethylation of histone H3 lysine 4 (H3K4me3) accumulates at promoters in a gene activity dependant manner. The Set1 complex is responsible for most H3K4me3 in somatic cells and contains the conserved subunit Cfp1, which is implicated in targeting the Set1 complex to CpG islands in mammals. In mouse embryonic stem cells, Cfp1 is necessary for H3K4me3 accumulation at constitutively active gene promoters, but is not required to maintain steady-state transcription of the associated gene. Here we show that Cfp1 is instrumental for targeting H3K4me3 at promoters upon rapid transcriptional induction in response to external stimuli. Surprisingly, H3K4me3 accumulation is not required to ensure appropriate transcriptional output but rather plays gene specific roles. We also show that Cfp1 dependant H3K4me3 deposition contributes to H3K9 acetylation genome wide; suggesting that Cfp1 dependant H3K4me3 regulates overall H3K9 acetylation dynamics and is necessary for histone acetyl transferase recruitment. Finally, we observe increased antisense transcription at start and end of genes that requires Cfp1 for accurate H3K4me3 and H3K9ac deposition. Our results assign a key role for Cfp1 in establishing a complex active promoter chromatin state and shed light on how chromatin signalling pathways provide context dependant outcomes. wt (wtES) or Cfp1-/- (Cfp1null) ES cells were treated or not with doxorubicin (Dox) at 1uM for 6h. H3K4me3 (2 replicates) and H3K9,K14ac (H3ac, 1 replicate) occupancy was analyzed in each condition by ChIP-Seq. Input DNA for each cell line was alos sequenced alongside.

2014-08-20 | E-GEOD-53490 | biostudies-arrayexpress

Cfp1 is required for gene expression dependent H3K4me3 and H3K9 acetylation in embryonic stem cells (RNA-Seq)

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2014-08-20 | E-GEOD-53489 | biostudies-arrayexpress

Cfp1 is required for gene expression dependent H3K4me3 and H3K9 acetylation in embryonic stem cells (ChIP-Seq)

2014-08-20 | GSE53490 | GEO

Cfp1 is required for gene expression dependent H3K4me3 and H3K9 acetylation in embryonic stem cells (RNA-Seq)

2014-08-20 | GSE53489 | GEO

Cfp1 is required for accurate H3K4me3 deposition in mouse ES cells

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2019-09-27 | PXD015548 | Pride

Genome-wide maps of CFP1, RNA Polymerase II and H3K4me3 in mouse brain.

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