Project description:Multi-dimensional histone modifications for coordinated regulation of gene expression under hypoxia or clioquinol (CQ) treatment [gene expression]
Project description:Methylation QTLs are associated with coordinated changes in transcription factor binding, histone modifications, and gene expression levels [Bisulfite-array]
Project description:We report the high-throughput profilings of HIF1 and histone modifications in human umbilical vein endothelial cells (HUVEC). By obtaining over two billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of HUVEC under normoxia and hypoxia. We find that HIF1binds to not only to transcriptional starting sites but also enhancer regions and that HIF1 binding sites were overlapped with lysine 4 trimethylatio, monomethylation and lysine 27 acetylation . Finally, we show that chromatin state can change under hypoxia by using chromatin conformational capture assay. This study provides novel insights into the interaction between HIF1 and KDM3A and also the epigenetic regulation of HIF1. Examination of HIF1 and 3 different histone modifications in HUVEC under 2 conditions. Related gene expression data is provided in GSE35932.
Project description: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.
Project description: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.
