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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE53489 | GEO | 2014/08/20

SECONDARY ACCESSION(S): PRJNA232119

REPOSITORIES: GEO

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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)

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 and rRNA depleted total RNA was prepraed and analyzed by strand-specific RNA-Seq in 2 biological and 2 technical replicates per condition.

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

Physical and functional interaction between SET1/COMPASS complex component CFP-1 and a Sin3S HDAC complex in C. elegans

Project description:The CFP1 CXXC zinc finger protein targets the SET1/COMPASS complex to nonmethylated CpG rich promoters to implement tri-methylation of histone H3 Lys4 (H3K4me3). Although H3K4me3 is widely associated with gene expression, the effects of CFP1 loss vary, suggesting additional chromatin factors contribute to context dependent effects. Using a proteomics approach, we identified CFP1 associated proteins and an unexpected direct link between C. elegans CFP-1 and an Rpd3/Sin3 small (SIN3S) histone deacetylase complex.

2019-09-27 | PXD015548 | Pride

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.

2017-09-05 | GSE93536 | GEO

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

2017-09-05 | GSE93428 | GEO

Analysis of non-methylated islands, sites of accessible chromatin and nascent transcriptome in C127 mouse cell line. [C127_BioCAP-ATAC-4sU]

2017-09-05 | GSE93427 | GEO

Gene expression changes upon deletion of CFP1 in mouse ES cells. [mESC_RNAseq]

2017-09-05 | GSE93537 | GEO

Physical and functional interaction between the SET1/COMPASS complex component CFP-1/CXXC and a Sin3S HDAC complex

Project description:The CFP1/CXXC protein targets SET1/COMPASS complexes to non-methylated CpG rich promoter regions to implement tri-methylation of histone H3 Ly4 (H3K4me3). Although H3K4me3 is widely associated with gene expression, the effects of CFP1 loss depend on chromatin context. Little is known about how CFP1 binding is coordinated with other chromatin factors. Using a proteomics approach, we establish a link between C. elegans CFP1 and a small Rpd3/Sin3 histone deacetylase (HDAC) complex (Sin3S). Mutants of CFP-1, SIN-3, and the catalytic subunit SET-2/SET1 have similar phenotypes and misregulate the expression of common genes. CFP-1 directly interacts with SIN-3 through a region including the conserved PAH1 domain, and contributes to recruitment of SIN-3 and the Sin3S subunit HDA-1 to H3K4me3 enriched promoters. Our results reveal a novel role for CFP-1 in mediating interaction between SET1/COMPASS and a Sin3 HDAC small complex at promoters, with implications for the coordinate regulation of gene expression by chromatin- associated complexes with distinct activities.

2019-09-29 | GSE114715 | GEO

Cfp1 is required for accurate H3K4me3 deposition in mouse ES cells

Project description:Trimethylation of histone H3 lysine 4 (H3K4me3) is a mark of active and poised promoters. The Set1 complex is responsible for most somatic H3K4me3 and contains the conserved subunit Cfp1, which binds to unmethylated CpGs and links H3K4me3 with CpG islands (CGIs). Here we report that Cfp1 plays unanticipated roles in organising genome wide H3K4me3 in embryonic stem cells. Cfp1-deficiency caused two contrasting phenotypes: drastic loss of H3K4me3 at expressed CGI-associated genes, with minimal consequences for transcription, and creation of ectopic H3K4me3 peaks at numerous regulatory regions. DNA binding by Cfp1 was dispensable for targeting H3K4me3 to active genes, but was required to prevent ectopic H3K4me3 peaks. We analysed gene expression in wild-type, Cfp1-/-, Cfp1wt rescue and Cfp1C169A rescue ES cells on the MouseWG-6 v2.0 Expression BeadChip (Illumina). We found that the presence of ectopic peaks at enhancers often coincided with increased expression of nearby genes. This suggests that CpG targeting prevents leakage of H3K4me3 to inappropriate chromatin compartments. Our results demonstrate that Cfp1 is a specificity factor that integrates multiple signals, including promoter CpG content and gene activity, to regulate genome-wide patterns of H3K4me3.

2012-07-04 | E-MTAB-1198 | biostudies-arrayexpress

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