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Search: L773:1465 6906 OR L773:1474 760X OR L773:1474 7596 > (2020-2024) > β-actin mediated H3...

  • 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 ...

  • 2023-01-25
  • Springer Science and Business Media LLC,2023
  • printrdacarrier

Numbers

  • 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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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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)
  • Gunsalus, Kristin C. (author)
  • Percipalle, PiergiorgioStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,New York University Abu Dhabi (NYUAD), United Arab Emirates(Swepub:su)pperc (author)
  • 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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NATURAL SCIENCES
NATURAL SCIENCES
and Biological Scien ...
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Genome Biology
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Stockholm University

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