Genome-wide maps of histone modifications in endometrial cancer cell lines
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA454106 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7079920.fastq.gz | Fastqsanger.gz | |||
| SRR7079930.fastq.gz | Fastqsanger.gz | |||
| SRR7079940.fastq.gz | Fastqsanger.gz | |||
| SRR7079921.fastq.gz | Fastqsanger.gz | |||
| SRR7079931.fastq.gz | Fastqsanger.gz |
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Project description:DNA regulatory elements are reported to be enriched for variants identified by genome-wide association studies to be significantly assocaited with risk of complext traits. Here, we have performed genome-wide mapping of histone modifications in two endometrial cancer cell lines and performed interestions of these sites with genetic risk variants identified by genome-wide association study of endometrial cancer. Histone modifications indicative of enhancers (H3K4Me1 and H3K27Ac) and promoters (H3K27Ac and H3K4Me3) were identified by ChIP-seq in Ishikawa and JHUEM-14 cells, pre- and post-stimulation by estrogen. Overall, 73% of endometrial cancer genetic risk variants overlapped at least histone modification site. This overlap was significantly greater than the overlap observed for these histone marks with genetic risk variants related to, for example, endometriosis (51%; Fisher’s Exact p = 8.7x10-8) or schizophrenia (40%; Fisher’s Exact p < 2.2x10-16). These findings indicate the relevance of the selected cell and tissue types for informing endometrial cancer biology. Overlaps between genetic risk variants and histone modification sites increased significantly after stimulation with estrogen (50% versus 38% for unstimulated features; Fisher’s Exact p = 5.6x10-3), emphasizing the importance of estrogen in endometrial cancer aetiology.
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Project description:Histone acetylation and methylation regulate gene expression in eukaryotes, but their effects on the transcriptome of a multicellular organism and on the transcriptomic divergence between species are still poorly understood. Here we present the first genome-wide 1-bp resolution maps of histone acetylation, histone methylation and core histone in Arabidopsis thaliana and a comprehensive analysis of these maps and gene expression data in A. thaliana, A. arenosa and allotetraploids. H3K9 acetylation (H3K9ac) and H3K4 trimethylation (H3K4me3) are correlated, and their high densities near transcriptional start sites determine constitutive expression of genes involved in translation. In contrast, broad distributions of these modifications toward coding regions determine expression variation, especially in genes involved in photosynthesis, carbohydrate metabolism, and defense responses. A dispersed distribution of H3K27me3 and depletion of H3K9ac and H3K4me3 are associated with developmentally repressed genes. Finally, genes affected by histone deacetylase mutation and species divergence tend to show high expression variation. In conclusion, changes in histone acetylation and methylation modulate developmental and environmental gene expression variation within and between species.
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Project description:Dramatic changes of gene expressions are known to occur in human endometrial stromal cells (ESC) during decidualization. The changes in gene expression are associated with changes of chromatin structure, which are regulated by epigenetic mechanisms such as histone modifications. Here, we investigated genome-wide changes in histone modifications and mRNA expressions associated with decidualization in human ESC using chromatin immunoprecipitation (ChIP) combined with next-generation sequencing. ESC were incubated with estradiol and medroxyprogesterone acetate for 14 days to induce decidualization. The ChIP-sequence data showed that induction of decidualization increased H3K27ac and H3K4me3 signals in many genomic regions but decreased in only a few regions. Most (80%) of the H3K27ac-increased regions and half of the H3K4me3-increased regions were located in the distal promoter regions (more than 3 kb upstream or downstream of the transcription start site). RNA-sequence showed that induction of decidualization up-regulated 881 genes, 223 of which had H3K27ac- or H3K4me3-increased regions in the proximal and distal promoter regions. Induction of decidualization increased the mRNA levels of these genes more than it increased the mRNA levels of genes without H3K27ac- or H3K4me3-increased regions. Pathway analysis revealed that up-regulated genes with the H3K27ac- or H3K4me3-increased regions were associated with insulin signaling. These results show that histone modification statuses genome-widely change in human ESC by induction of decidualization. The main changes of histone modifications are increases of H3K27ac and H3K4me3 in both the proximal and distal promoter regions, which are involved in the up-regulation of gene expression that occurs during decidualization. mRNA profiles of human endometrial stromal cells with and without EP inductions for 2 individuals. (EP induction: induction with estradiol (10-8 M) and medroxyprogesterone acetate (10-6 M))
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