BAZ2A safeguards genome architecture of ground-state pluripotent stem cells
Dalcher, Damian; Tan, Jennifer Yihong; Bersaglieri, Cristiana; Peña-Hernández, Rodrigo; Vollenweider, Eva; Zeyen, Stefan; Schmid, Marc W; Bianchi, Valerio; Butz, Stefan; Roganowicz, Marcin; Kuzyakiv, Rostyslav; Baubec, Tuncay; Marques, Ana Claudia; Santoro, Raffaella
(2020) EMBO Journal, volume 39, issue 23, pp. 1 - 23
(Article)
Abstract
Chromosomes have an intrinsic tendency to segregate into compartments, forming long-distance contacts between loci of similar chromatin states. How genome compartmentalization is regulated remains elusive. Here, comparison of mouse ground-state embryonic stem cells (ESCs) characterized by open and active chromatin, and advanced serum ESCs with a more closed and repressed
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genome, reveals distinct regulation of their genome organization due to differential dependency on BAZ2A/TIP5, a component of the chromatin remodeling complex NoRC. On ESC chromatin, BAZ2A interacts with SNF2H, DNA topoisomerase 2A (TOP2A) and cohesin. BAZ2A associates with chromatin sub-domains within the active A compartment, which intersect through long-range contacts. We found that ground-state chromatin selectively requires BAZ2A to limit the invasion of active domains into repressive compartments. BAZ2A depletion increases chromatin accessibility at B compartments. Furthermore, BAZ2A regulates H3K27me3 genome occupancy in a TOP2A-dependent manner. Finally, ground-state ESCs require BAZ2A for growth, differentiation, and correct expression of developmental genes. Our results uncover the propensity of open chromatin domains to invade repressive domains, which is counteracted by chromatin remodeling to establish genome partitioning and preserve cell identity.
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Keywords: BAZ2A, genome organization, ground-state embryonic stem cells, H3K27me3, Topoisomerase 2A, General Biochemistry,Genetics and Molecular Biology, General Immunology and Microbiology, Molecular Biology, General Neuroscience, Journal Article
ISSN: 0261-4189
Publisher: Springer Science and Business Media Deutschland GmbH
Note: Funding Information: This work was supported by the Swiss National Science Foundation (310003A‐152854 and 31003A_173056 to R.S.; PP00P3_150667 to A.C.M.; NCCR RNA & Disease to R.S and to A.C.M.; 157488 and 180345 to T.B.), ERC grant (ERC‐AdG‐787074‐NucleolusChromatin to RS), Forschungskredit of the University of Zurich (to D.D, E.V., and M.R.), UBS Promedica Stiftung, Julius Müller Stiftung, Olga Mayenfisch Stifung, Sassella Stiftung, and Stiftung für wissenschaftliche Forschung an der Universität Zürich (to R.S.). We thank Peter Hunziker, Catherine Aquino, and the Functional Genomic Center Zurich for the assistance in sequencing and proteomic analysis. We also thank Dominik Bär for technical assistance. We thank C. Ciaudo for having provided ESC lines. Funding Information: This work was supported by the Swiss National Science Foundation (310003A-152854 and 31003A_173056 to R.S.; PP00P3_150667 to A.C.M.; NCCR RNA & Disease to R.S and to A.C.M.; 157488 and 180345 to T.B.), ERC grant (ERC-AdG-787074-NucleolusChromatin to RS), Forschungskredit of the University of Zurich (to D.D, E.V., and M.R.), UBS Promedica Stiftung, Julius M?ller Stiftung, Olga Mayenfisch Stifung, Sassella Stiftung, and Stiftung f?r wissenschaftliche Forschung an der Universit?t Z?rich (to R.S.). We thank Peter Hunziker, Catherine Aquino, and the Functional Genomic Center Zurich for the assistance in sequencing and proteomic analysis. We also thank Dominik B?r for technical assistance. We thank C. Ciaudo for having provided ESC lines. Publisher Copyright: © 2020 The Authors. Published under the terms of the CC BY NC ND 4.0 license Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
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