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PMID:23516383

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Citation

Ma, P and Schultz, RM (2013) Histone Deacetylase 2 (HDAC2) Regulates Chromosome Segregation and Kinetochore Function via H4K16 Deacetylation during Oocyte Maturation in Mouse. PLoS Genet. 9:e1003377

Abstract

Changes in histone acetylation occur during oocyte development and maturation, but the role of specific histone deacetylases in these processes is poorly defined. We report here that mice harboring Hdac1 (-/+)/Hdac2 (-/-) or Hdac2 (-/-) oocytes are infertile or sub-fertile, respectively. Depleting maternal HDAC2 results in hyperacetylation of H4K16 as determined by immunocytochemistry-normal deacetylation of other lysine residues of histone H3 or H4 is observed-and defective chromosome condensation and segregation during oocyte maturation occurs in a sub-population of oocytes. The resulting increased incidence of aneuploidy likely accounts for the observed sub-fertility of mice harboring Hdac2 (-/-) oocytes. The infertility of mice harboring Hdac1 (-/+)/Hdac2 (-/-)oocytes is attributed to failure of those few eggs that properly mature to metaphase II to initiate DNA replication following fertilization. The increased amount of acetylated H4K16 likely impairs kinetochore function in oocytes lacking HDAC2 because kinetochores in mutant oocytes are less able to form cold-stable microtubule attachments and less CENP-A is located at the centromere. These results implicate HDAC2 as the major HDAC that regulates global histone acetylation during oocyte development and, furthermore, suggest HDAC2 is largely responsible for the deacetylation of H4K16 during maturation. In addition, the results provide additional support that histone deacetylation that occurs during oocyte maturation is critical for proper chromosome segregation.

Links

PubMed PMC3597510 Online version:10.1371/journal.pgen.1003377

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:HDAC2

enables

GO:0034739: histone deacetylase activity (H4-K16 specific)

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:HDAC2

GO:0034739: histone deacetylase activity (H4-K16 specific)

ECO:0000315:

F

fig4. C and D show that H4K16 acetylation is greatly increased in Hdac-/- knockouts compared to wild type in mouse oocytes. fig4.C shows Immunocytochemical detection of HDAC1 and histone H4K16 acetylation, and fig4.D shows the quantification of the data from C.

complete
CACAO 7900


See also

References

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