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β-actin mediated H3...
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Mahmood, Syed Raza
(author)
β-actin mediated H3K27ac changes demonstrate the link between compartment switching and enhancer-dependent transcriptional regulation
- Article/chapterEnglish2023
Publisher, publication year, extent ...
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2023-01-25
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Springer Science and Business Media LLC,2023
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Numbers
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LIBRIS-ID:oai:DiVA.org:su-215181
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https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-215181URI
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https://doi.org/10.1186/s13059-023-02853-9DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Background: Recent work has demonstrated that three-dimensional genome organization is directly affected by changes in the levels of nuclear cytoskeletal proteins such as β-actin. The mechanisms which translate changes in 3D genome structure into changes in transcription, however, are not fully understood. Here, we use a comprehensive genomic analysis of cells lacking nuclear β-actin to investigate the mechanistic links between compartment organization, enhancer activity, and gene expression.Results: Using HiC-Seq, ATAC-Seq, and RNA-Seq, we first demonstrate that transcriptional and chromatin accessibility changes observed upon β-actin loss are highly enriched in compartment-switching regions. Accessibility changes within compartment switching genes, however, are mainly observed in non-promoter regions which potentially represent distal regulatory elements. Our results also show that β-actin loss induces widespread accumulation of the enhancer-specific epigenetic mark H3K27ac. Using the ABC model of enhancer annotation, we then establish that these epigenetic changes have a direct impact on enhancer activity and underlie transcriptional changes observed upon compartment switching. A complementary analysis of fibroblasts undergoing reprogramming into pluripotent stem cells further confirms that this relationship between compartment switching and enhancer-dependent transcriptional change is not specific to β-actin knockout cells but represents a general mechanism linking compartment-level genome organization to gene expression.Conclusions: We demonstrate that enhancer-dependent transcriptional regulation plays a crucial role in driving gene expression changes observed upon compartment-switching. Our results also reveal a novel function of nuclear β-actin in regulating enhancer function by influencing H3K27 acetylation levels.
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El Said, Nadine Hosny
(author)
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Gunsalus, Kristin C.
(author)
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Percipalle, PiergiorgioStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,New York University Abu Dhabi (NYUAD), United Arab Emirates(Swepub:su)pperc
(author)
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Stockholms universitetInstitutionen för molekylär biovetenskap, Wenner-Grens institut
(creator_code:org_t)
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In:Genome Biology: Springer Science and Business Media LLC241465-69061474-760X
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