TY - JOUR
T1 - β-actin dependent chromatin remodeling mediates compartment level changes in 3D genome architecture
AU - Mahmood, Syed Raza
AU - Xie, Xin
AU - Hosny El Said, Nadine
AU - Venit, Tomas
AU - Gunsalus, Kristin C.
AU - Percipalle, Piergiorgio
N1 - Funding Information:
We thank Nizar Drou, Marc Arnoux, and Mehar Sultana from the genomics core facilities at NYU Abu Dhabi, Center for Genomics and Systems Biology for technical help. We thank Christophe Ampe (University of Gent, Belgium) for kindly providing us with the β-actin +/+, β-actin +/−, and β-actin −/− MEFs. This work is supported by grants from New York University Abu Dhabi, the Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences, the Swedish Research Council (Vetenskapsrådet), and the Swedish Cancer Society (Cancerfonden).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - β-actin is a crucial component of several chromatin remodeling complexes that control chromatin structure and accessibility. The mammalian Brahma-associated factor (BAF) is one such complex that plays essential roles in development and differentiation by regulating the chromatin state of critical genes and opposing the repressive activity of polycomb repressive complexes (PRCs). While previous work has shown that β-actin loss can lead to extensive changes in gene expression and heterochromatin organization, it is not known if changes in β-actin levels can directly influence chromatin remodeling activities of BAF and polycomb proteins. Here we conduct a comprehensive genomic analysis of β-actin knockout mouse embryonic fibroblasts (MEFs) using ATAC-Seq, HiC-seq, RNA-Seq and ChIP-Seq of various epigenetic marks. We demonstrate that β-actin levels can induce changes in chromatin structure by affecting the complex interplay between chromatin remodelers such as BAF/BRG1 and EZH2. Our results show that changes in β-actin levels and associated chromatin remodeling activities can not only impact local chromatin accessibility but also induce reversible changes in 3D genome architecture. Our findings reveal that β-actin-dependent chromatin remodeling plays a role in shaping the chromatin landscape and influences the regulation of genes involved in development and differentiation.
AB - β-actin is a crucial component of several chromatin remodeling complexes that control chromatin structure and accessibility. The mammalian Brahma-associated factor (BAF) is one such complex that plays essential roles in development and differentiation by regulating the chromatin state of critical genes and opposing the repressive activity of polycomb repressive complexes (PRCs). While previous work has shown that β-actin loss can lead to extensive changes in gene expression and heterochromatin organization, it is not known if changes in β-actin levels can directly influence chromatin remodeling activities of BAF and polycomb proteins. Here we conduct a comprehensive genomic analysis of β-actin knockout mouse embryonic fibroblasts (MEFs) using ATAC-Seq, HiC-seq, RNA-Seq and ChIP-Seq of various epigenetic marks. We demonstrate that β-actin levels can induce changes in chromatin structure by affecting the complex interplay between chromatin remodelers such as BAF/BRG1 and EZH2. Our results show that changes in β-actin levels and associated chromatin remodeling activities can not only impact local chromatin accessibility but also induce reversible changes in 3D genome architecture. Our findings reveal that β-actin-dependent chromatin remodeling plays a role in shaping the chromatin landscape and influences the regulation of genes involved in development and differentiation.
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U2 - 10.1038/s41467-021-25596-2
DO - 10.1038/s41467-021-25596-2
M3 - Article
C2 - 34475390
AN - SCOPUS:85114621450
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5240
ER -