ArticleProceedings of the National Academy of Sciences of the United States of America2019
Mesoscale modeling reveals formation of an epigenetically driven HOXC gene hub.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50 citing papers in PubMed, 81 citations in OpenAlex.
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3 authors at 2 institutions in 2 countries.
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Abstract
Gene expression is orchestrated at the structural level by nucleosome positioning, histone tail acetylation, and linker histone (LH) binding. Here, we integrate available data on nucleosome positioning, nucleosome-free regions (NFRs), acetylation islands, and LH binding sites to "fold" in silico the 55-kb HOXC gene cluster and investigate the role of each feature on the gene's folding. The gene cluster spontaneously forms a dynamic connection hub, characterized by hierarchical loops which accommodate multiple contacts simultaneously and decrease the average distance between promoters by ∼100 nm. Contact probability matrices exhibit "stripes" near promoter regions, a feature associated with transcriptional regulation. Interestingly, while LH proteins alone decrease long-range contacts and acetylation alone increases transient contacts, combined LH and acetylation produce long-range contacts. Thus, our work emphasizes how chromatin architecture is coordinated strongly by epigenetic factors and opens the way for nucleosome resolution models incorporating epigenetic modifications to understand and predict gene activity.
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