BAZ2A safeguards genome architecture of ground-state pluripotent stem cells.

Details

Serval ID
serval:BIB_6BA59E7C8636
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
BAZ2A safeguards genome architecture of ground-state pluripotent stem cells.
Journal
The EMBO journal
Author(s)
Dalcher D., Tan J.Y., Bersaglieri C., Peña-Hernández R., Vollenweider E., Zeyen S., Schmid M.W., Bianchi V., Butz S., Roganowicz M., Kuzyakiv R., Baubec T., Marques A.C., Santoro R.
ISSN
1460-2075 (Electronic)
ISSN-L
0261-4189
Publication state
Published
Issued date
01/12/2020
Peer-reviewed
Oui
Volume
39
Number
23
Pages
e105606
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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 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.
Keywords
Adenosine Triphosphatases/metabolism, Animals, Cell Cycle Proteins, Cell Differentiation, Chromatin/metabolism, Chromatin Assembly and Disassembly, Chromosomal Proteins, Non-Histone/genetics, Chromosomal Proteins, Non-Histone/metabolism, DNA Topoisomerases, Type II/metabolism, Epigenomics, Gene Expression Regulation, Genome, Histones/metabolism, Mice, Mouse Embryonic Stem Cells/cytology, Pluripotent Stem Cells/cytology, Pluripotent Stem Cells/metabolism, Poly-ADP-Ribose Binding Proteins/metabolism, Cohesins, BAZ2A, H3K27me3, Topoisomerase 2A, genome organization, ground‐state embryonic stem cells
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2021 10:01
Last modification date
16/04/2024 7:11
Usage data