Trimethylation of histone H3 at lysine 4 (H3K4me3) is a marker of active promoters. Broad H3K4me3 promoter domains have been associated with cell type identity, but H3K4me3 dynamics upon cellular stress have not been well characterized. We assessed this by exposing endometrial stromal cells to hypoxia, which is a major cellular stress condition. We observed that hypoxia modifies the existing H3K4me3 marks and that promoter H3K4me3 breadth rather than height correlates with transcription. Broad H3K4me3 domains mark genes for endometrial core functions and are maintained or selectively extended upon hypoxia. Hypoxic extension of H3K4me3 breadth associates with stress adaptation genes relevant for the survival of endometrial cells including transcription factor KLF4, for which we found increased protein expression in the stroma of endometriosis lesions. These results substantiate the view on broad H3K4me3 as a marker of cell identity genes and reveal participation of H3K4me3 extension in cellular stress adaptation.
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http://dx.doi.org/10.1016/j.isci.2022.104235 | DOI Listing |
Nucleic Acids Res
May 2024
Department of Cardiovascular Genomics and Epigenomics, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
The limited regenerative capacity of the human heart contributes to high morbidity and mortality worldwide. In contrast, zebrafish exhibit robust regenerative capacity, providing a powerful model for studying how to overcome intrinsic epigenetic barriers maintaining cardiac homeostasis and initiate regeneration. Here, we present a comprehensive analysis of the histone modifications H3K4me1, H3K4me3, H3K27me3 and H3K27ac during various stages of zebrafish heart regeneration.
View Article and Find Full Text PDFTrimethylation of histone H3 at lysine 4 (H3K4me3) is a marker of active promoters. Broad H3K4me3 promoter domains have been associated with cell type identity, but H3K4me3 dynamics upon cellular stress have not been well characterized. We assessed this by exposing endometrial stromal cells to hypoxia, which is a major cellular stress condition.
View Article and Find Full Text PDFComput Struct Biotechnol J
December 2021
Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County 350, Taiwan, ROC.
The results of conventional gene-based analyses which combine epigenome and transcriptome data, including those conducted by the ENCODE/modENCODE projects, suggest various histone modifications performing regulatory functions in controlling mRNA expression (referred to as a histone code) in several model animals. While some histone codes were found to be universally adopted across organisms, "species-specific" histone codes have also been defined. We found that the characterization of these histone codes was confounded by factors (e.
View Article and Find Full Text PDFNPJ Genom Med
August 2021
School of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China.
Trimethylation of histone H3 lysine 27 trimethylation (H3K27me3) may be recruited by repressive Polycomb complexes to mediate gene silencing, which is critical for maintaining embryonic stem cell pluripotency and differentiation. However, the roles of aberrant H3K27me3 patterns in tumorigenesis are not fully understood. Here, we discovered that grand silencer domains (breadth > 50 kb) for H3K27me3 were significantly associated with epithelial cell differentiation and exhibited high gene essentiality and conservation in human esophageal epithelial cells.
View Article and Find Full Text PDFGenome Res
July 2022
Aix-Marseille University, Inserm, Theories and Approaches of Genomic Complexity (TAGC), UMR1090, 13288 Marseille, France.
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