BAZ2A safeguards genome architecture of ground‐state pluripotent stem cells

Autor: Marc W. Schmid, Tuncay Baubec, Raffaella Santoro, Damian Dalcher, Ana C. Marques, Rostyslav Kuzyakiv, Stefan Butz, Valerio Bianchi, Jennifer Y. Tan, Cristiana Bersaglieri, Marcin Roganowicz, Rodrigo Peña-Hernández, Stefan Zeyen, Eva Vollenweider
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Epigenomics
Pluripotent Stem Cells
ground‐state embryonic stem cells
Chromosomal Proteins
Non-Histone
H3K27me3
Cell Cycle Proteins
Biology
Regenerative Medicine
Genome
Chromatin
Epigenetics
Genomics & Functional Genomics
General Biochemistry
Genetics and Molecular Biology
Chromatin remodeling
Article
BAZ2A
Histones
03 medical and health sciences
Mice
0302 clinical medicine
Compartment (development)
Animals
genome organization
Induced pluripotent stem cell
Poly-ADP-Ribose Binding Proteins
Topoisomerase 2A
Molecular Biology
030304 developmental biology
Genomic organization
Adenosine Triphosphatases
0303 health sciences
General Immunology and Microbiology
Cohesin
General Neuroscience
Cell Differentiation
Mouse Embryonic Stem Cells
Articles
Chromatin Assembly and Disassembly
Embryonic stem cell
Chromatin
Cell biology
DNA Topoisomerases
Type II
Gene Expression Regulation
Development & Differentiation
030217 neurology & neurosurgery
Zdroj: The EMBO Journal
ISSN: 1460-2075
0261-4189
Popis: 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.
The NoRC chromatin remodeller subunit BAZ2A restricts active chromatin compartments and secures developmental gene expression in ESCs.
Databáze: OpenAIRE
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