Epigenetic dysregulation by nickel through repressive chromatin domain disruption
| Autor: | Beisi Xu, Darson Lai, Dustin E. Schones, Suresh Cuddapah, Takamitsu Hattori, Ramya K. Mallela, Cynthia C. Jose, Shohei Koide, Candi Trac, Lakshmanan Jagannathan |
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| Rok vydání: | 2014 |
| Předmět: |
CCCTC-Binding Factor
Euchromatin Blotting Western Bronchi Methylation Chromatin remodeling Cell Line Epigenesis Genetic Histones Histone H3 Nickel Humans Histone code Amino Acid Sequence Promoter Regions Genetic ChIA-PET Oligonucleotide Array Sequence Analysis Genetics Binding Sites Multidisciplinary biology Genome Human Gene Expression Profiling Lysine Acetylation Epithelial Cells Biological Sciences Chromatin Repressor Proteins Histone CTCF biology.protein RNA Interference Protein Binding |
| Zdroj: | Proceedings of the National Academy of Sciences. 111:14631-14636 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1406923111 |
| Popis: | Investigations into the genomic landscape of histone modifications in heterochromatic regions have revealed histone H3 lysine 9 dimethylation (H3K9me2) to be important for differentiation and maintaining cell identity. H3K9me2 is associated with gene silencing and is organized into large repressive domains that exist in close proximity to active genes, indicating the importance of maintenance of proper domain structure. Here we show that nickel, a nonmutagenic environmental carcinogen, disrupted H3K9me2 domains, resulting in the spreading of H3K9me2 into active regions, which was associated with gene silencing. We found weak CCCTC-binding factor (CTCF)-binding sites and reduced CTCF binding at the Ni-disrupted H3K9me2 domain boundaries, suggesting a loss of CTCF-mediated insulation function as a potential reason for domain disruption and spreading. We furthermore show that euchromatin islands, local regions of active chromatin within large H3K9me2 domains, can protect genes from H3K9me2-spreading-associated gene silencing. These results have major implications in understanding H3K9me2 dynamics and the consequences of chromatin domain disruption during pathogenesis. |
| Databáze: | OpenAIRE |
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