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- Mahmood, Syed Raza (författare)
β-actin mediated H3K27ac changes demonstrate the link between compartment switching and enhancer-dependent transcriptional regulation
- Artikel/kapitelEngelska2023
Förlag, utgivningsår, omfång ...
- 2023-01-25
- Springer Science and Business Media LLC,2023
- printrdacarrier
Nummerbeteckningar
- LIBRIS-ID:oai:DiVA.org:su-215181
- https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-215181URI
- https://doi.org/10.1186/s13059-023-02853-9DOI
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- Språk:engelska
- Sammanfattning på:engelska
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- SwePubSwePub
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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.
Ämnesord och genrebeteckningar
- NATURVETENSKAP Biologi hsv//swe
- NATURAL SCIENCES Biological Sciences hsv//eng
- 3D genome organization
- Enhancer regulation
- Transcriptional regulation
- Nuclear actin
Biuppslag (personer, institutioner, konferenser, titlar ...)
- El Said, Nadine Hosny (författare)
- Gunsalus, Kristin C. (författare)
- Percipalle, PiergiorgioStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,New York University Abu Dhabi (NYUAD), United Arab Emirates(Swepub:su)pperc (författare)
- Stockholms universitetInstitutionen för molekylär biovetenskap, Wenner-Grens institut (creator_code:org_t)
Sammanhörande titlar
- Ingår i:Genome Biology: Springer Science and Business Media LLC241465-69061474-760X
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