ChIP-seq analysis of CFP1 and related molecules
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE114084 | GEO | 2018/10/15
REPOSITORIES: GEO
Similar Datasets
Project description:ChIP-seq analysis of CFP1 and related molecules
| PRJNA464248 | ENA
Project description:Spermatogenesis is a complex process involving meiosis in spermatocytes and dynamic epigenetic changes that ensure the inheritance of genetic traits. CXXC finger protein 1 (Cfp1), a component of the SETD1 methyltransferase complex, has a binding domain specific for unmethylated CpG sites. Previous studies have implicated Cfp1 in the epigenetic changes required for meiosis in spermatocytes, and its loss of function has been shown to result in male sterility. In this study, we aimed to gain a comprehensive understanding of Cfp1 function in spermatocytes by examining its genome-wide binding profile and the resulting changes in DNA methylation and H3K4me3, a histone modification associated with active gene transcription. We isolated Cfp1-depleted spermatocytes and performed H3K4me3 ChIP-seq and reduced-representation bisulfite sequencing (RRBS) analyses. By integrating these multi-omics datasets with Cfp1 ChIP-seq analysis, we identified genes directly regulated by Cfp1 and characterised the epigenetic changes associated with its regulation. Our analysis shows that Cfp1 not only directly affects the regulation of genes essential for meiosis, but also has a significant impact on the overall regulation of gene expression. The knowledge gained from studying the regulatory mechanisms of Cfp1 in spermatocytes provides valuable information about the reproductive process and contributes to our understanding of the underlying causes of infertility.
2023-08-10 | GSE240280 | GEO
Project description:Meiosis occurs specifically in germ cells to produce sperm and oocytes that are competent for sexual reproduction. Multiple factors are required for successful meiotic entry, progression, and termination. Trimethylation of histone H3 on lysine 4 (H3K4me3), a mark of active transcription, has been implicated in spermatogenesis by forming double strand breaks (DSBs). The role of H3K4me in transcriptional regulation during meiosis however, remains poorly understood. Here, we reveal that mouse CXXC finger protein 1 (Cfp1), a component of H3K4me methyltransferases Setd1a/b, is dynamically expressed in differentiating male germ cells and safeguards meiosis by controlling gene expression. Depletion of Cfp1 in male germ cells resulted in infertility with reduced H3K4me3, spermatogenic arrest, and repression of essential germ cell development and meiosis genes. Importantly, ChIP-Seq analysis revealed that Cfp1 is mainly enriched at transcriptional start sites to promote gene expression and H3K4me2/3 levels at pachytene stage. The most highly enriched genes were associated with meiosis and homologous recombination during differentiation of spermatocytes to round spermatids. Additionally, missense mutations of human CFP1 were prevalent in patients with nonobstructive azoospermia. Therefore, our study establishes a mechanistic link between CFP1-mediated transcriptional control and meiotic progression, and provides unprecedented genetic basis for understanding human sterility.
2018-10-10 | GSE120994 | GEO
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
Project description:Through RNA-seq of wildtype and CFP1-deleted GV oocytes of different ages, zygotes and 2-cell embryos and whole genome bisulfite sequencing of GV oocytes, We show here that CFP1 is responsible for epigenetic maturation in oocytes. Deletion of CFP1 directly decreased histone H3K4 trimethylation and caused global down-regulation of gene expression in oocytes.These genes are involved in cytoplasmic lattice formation, maternal-zygotic transition and epigenetic maturation. Maternal CFP1-deleted oocytes had fewer CPLs in the cytoplasm and the organelles were severely aggregated, which further caused defects in α-tubulin polymerization and aneuploidy in meiosis II. The genome was less methylated and methylation of maternal DNA was impaired after CFP1 deletion. Therefore CFP1-deleted oocytes fail to complete epigenetic maturation as well as cytoplasmic maturation and nuclear maturation and unable to gain developmental competence during oogenesis.
2017-09-30 | GSE85019 | GEO
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
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
Project description:We report the application of single molecule-based sequencing technology for high-throughput mapping of CFP1, RNA polymerase II and H3K4me3 in mouse brain. By obtaining sequence from chromatin immunoprecipitated DNA, we generated genome-wide binding / chromatin-state maps for mouse brain. We find a good correlation between CFP1 binding and H3K4me3 consistent with it presence in the SetD1 histone methylatransferase complex. Mapped RNA polymerase II colocalised with the majority of CFP1 / H3K4me3 positive CpG islands but not all. This study provides a comprehensive characterisation of the genome wide distribution of a previously uncharacaterised DNA binding factor and suggests a link between DNA base composition and chromatin state. Examination of H3K4me3, RNA PolymeraseII and CFP1 in mouse brain.
2010-04-15 | E-GEOD-18578 | biostudies-arrayexpress
Project description:Cardiomyocyte maturation is the final stage of heart development, and abnormal cardiomyocyte maturation will lead to serious heart diseases. CXXC zinc finger protein 1 (Cfp1) is an important epigenetic factor, which plays an essential role in the development and maturation of multi-lineage cells, while its effect on the maturation of cardiomyocyte remains unclear. This study was performed to explore the potential role of Cfp1 in cardiomyocyte maturation of heart and the underlying mechanisms. Cardiomyocyte-specific Cfp1 knockout (Cfp1-cKO) mice died within 4 weeks of birth. Cardiomyocytes from Cfp1-cKO mice showed an inhibited maturation phenotype in structure, metabolism, contractile function, and cell cycle, accompanied by down-regulation of adult genes and up-regulation of fetal genes. In contrast, cardiomyocyte-specific Cfp1 transgenic (Cfp1-TG) mice and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) overexpressing Cfp1 showed a more mature phenotype. Mechanistically, deficiency of Cfp1 results in reduced trimethylation on lysine 4 of histone H3 (H3K4me3) modification and formation of ectopic H3K4me3. Moreover, Cfp1 deletion decreased the level of H3K4me3 modification in adult genes and increased the level of H3K4me3 modification in fetal genes. Collectively, Cfp1 modulates the expression of cardiomyocyte maturation related genes by modulating histone H3K4me3 modification, which in turn regulates cardiomyocyte maturation. This study implicates Cfp1 as an important molecule regulating cardiomyocyte maturation, and its dysfunction is strongly associated with cardiac disease.
2024-03-27 | GSE240852 | GEO
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