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Hypoxia-driven histone modifications govern gene regulation for mature eye lens formation [CUT&Run]

ABSTRACT: Evidence suggests that the hypoxic environment of the lens regulates the expression of genes required for lens formation and function. Here, we tested the hypothesis that hypoxia regulates these genes through induction of specific histone modifications. Global levels of hypoxia induced histone modifications were determined in cultured day 13 chick lenses exposed to 1% oxygen. The genome-wide localizations of H3K27ac and H3K4me3 were identified by CUT&RUN analysis and mapped to within 5kb of the transcriptional start sites of genes activated or repressed by hypoxia identified by RNA Seq. The requirement for these histone modifications for hypoxia induced gene expression was determined using inhibitors of histone writers and erasers. The levels of activating modifications H3K4me3, H3K9ac, H3K14ac and H3K27ac in hypoxia treated lenses increased while levels of repressive modifications H3K9me3 and H3K27me3 remained unchanged. Hypoxia-specific H3K4me3 and/or H3K27ac regions were detected within 5 kb of the transcriptional start sites of over 900 fiber cell genes with increased expression upon hypoxia exposure and 350 genes with decreased expression. Inhibition of histone writers and erasers resulted in altered levels of key fiber cell genes upon hypoxia exposure. The results provide evidence that hypoxia induced histone modifications regulate genes required for mature lens formation and they provide a framework for understanding the role of hypoxia specific histone modifications in the regulation of genes in more complex tissues.

ORGANISM(S): Gallus gallus

PROVIDER: GSE309116 | GEO | 2025/12/02

REPOSITORIES: GEO

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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. Examination of 4 different histone modifications in human endometrial stromal cells with or without EP inductions for 2 individuals. (EP induction: induction with estradiol (10-8 M) and medroxyprogesterone acetate (10-6 M))

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Hypoxia-driven histone modifications govern gene regulation for mature eye lens formation [CUT&Run]

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