Abstract
Abstractβ-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.
Funder
Vetenskapsrådet
Cancerfonden
New York University Abu Dhabi
Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
Reference69 articles.
1. Bonev, B. & Cavalli, G. Organization and function of the 3D genome. Nat. Rev. Genet. 17, 661 (2016).
2. Xie, X. et al. Beta-Actin-dependent global chromatin organization and gene expression programs control cellular identity. FASEB J. 32, 1296–1314 (2018).
3. Ondrej, V., Lukasova, E., Krejci, J., Matula, P. & Kozubek, S. Lamin A/C and polymeric actin in genome organization. Mol. Cells 26, 356–361 (2008).
4. Miroshnikova, Y. A., Nava, M. M. & Wickström, S. A. Emerging roles of mechanical forces in chromatin regulation. J. Cell Sci. 130, 2243–2250 (2017).
5. Spichal, M. & Fabre, E. The emerging role of the cytoskeleton in chromosome dynamics. Front. Genet. 8, https://doi.org/10.3389/fgene.2017.00060 (2017).
Cited by
28 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献