KAT7/HBO1/MYST2 Regulates CENP-A Chromatin Assembly by Antagonizing Suv39h1-Mediated Centromere Inactivation.

Centromere chromatin containing histone H3 variant CENP-A is required for accurate chromosome segregation as a foundation for kinetochore assembly. Human centromere chromatin assembles on a part of the long α-satellite (alphoid) DNA array, where it is flanked by pericentric heterochromatin. Heterochromatin spreads into adjacent chromatin and represses gene expression, and ...
it can antagonize centromere function or CENP-A assembly. Here, we demonstrate an interaction between CENP-A assembly factor M18BP1 and acetyltransferase KAT7/HBO1/MYST2. Knocking out KAT7 in HeLa cells reduced centromeric CENP-A assembly. Mitotic chromosome misalignment and micronuclei formation increased in the knockout cells and were enhanced when the histone H3-K9 trimethylase Suv39h1 was overproduced. Tethering KAT7 to an ectopic alphoid DNA integration site removed heterochromatic H3K9me3 modification and was sufficient to stimulate new CENP-A or histone H3.3 assembly. Thus, KAT7-containing acetyltransferases associating with the Mis18 complex provides competence for histone turnover/exchange activity on alphoid DNA and prevents Suv39h1-mediated heterochromatin invasion into centromeres.
Mesh Terms:
Autoantigens, Centromere, Centromere Protein A, Chromatin Assembly and Disassembly, Chromosomal Proteins, Non-Histone, Chromosome Segregation, DNA-Binding Proteins, G1 Phase, Gene Knockout Techniques, HeLa Cells, Histone Acetyltransferases, Histones, Humans, Lysine, Methylation, Methyltransferases, Multiprotein Complexes, Nuclear Proteins, Protein Stability, Protein Subunits, Repressor Proteins, Trans-Activators
Dev. Cell
Date: Dec. 06, 2015
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