Histones, nuclear proteins that bind DNA and form nucleosomes, are directly involved with both
the packaging of DNA into chromosomes and the regulation of transcription. Histone
acetylation/deacetylation is a major factor in regulating chromatin structural dynamics during
transcription.
NCBI Summary:
This gene product belongs to the histone deacetylase family. Histone deacetylases act via the formation of large multiprotein complexes, and are responsible for the deacetylation of lysine residues at the N-terminal regions of core histones (H2A, H2B, H3 and H4). This protein forms transcriptional repressor complexes by associating with many different proteins, including YY1, a mammalian zinc-finger transcription factor. Thus, it plays an important role in transcriptional regulation, cell cycle progression and developmental events. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]
General function
Cell death/survival, Apoptosis, DNA Replication
, Epigenetic modifications
Nucleolar Translocation of Histone Deacetylase 2 Is Involved in Regulation of Transcriptional Silencing in the Cat Germinal Vesicle. Lee PC et al. (2015) Histone deacetylase 2 (HDAC2) is a key transcriptional co-regulator that is suspected to play a role during oogenesis. It is known that RNA transcription in the cat germinal vesicle (GV) stops during folliculogenesis at the late antral follicle stage and is unrelated to histone deacetylation or chromatin condensation. The objective of the present study was to determine if and how HDAC2 participates in transcription regulation in the cat GV. Spatiotemporal HDAC2 protein expression was examined by immunostaining oocytes from primary to large antral follicles. HDAC2 was detected in the majority of GVs within oocytes from early, small, and large antral follicles. At early and small antral stages, HDAC2 was found primarily in the GV's nucleoplasm. There then was a significant shift in HDAC2 localization into the nucleolus, mostly in oocytes from large antral follicles. Assessments revealed that transcription was active in oocytes that contained nucleoplasm-localized HDAC2, whereas nucleolar-bound HDAC2 was associated with loss of both global transcription and ribosomal RNA presence at all antral stages. When oocytes were exposed to the HDAC inhibitor valproic acid, results indicated that HDAC regulated transcriptional activity in the nucleoplasm, but not in the nucleolus. Collective results suggest that nucleolar translocation of HDAC2 is associated with transcriptional silencing in the GV, thereby likely contributing to an oocyte's acquisition of competence.//////////////////
Transcription Profile of Candidate Genes for the Acquisition of Competence During Oocyte Growth in Cattle. Bessa I et al. The aim of this study was to investigate the expression profile of candidate genes involved in competence during oocyte growth. The candidate genes (BMP15, OOSP1, H1FOO, H2A, H3A, H4, SLBP, DNMT1, DNMT3B, HAT1, HDAC2 and SUV39H1) were selected because of their possible involvement in determining oocyte developmental competence. Pre-antral and antral follicles were isolated from the ovaries of Zebu (Bos indicus) cows, measured and classified into the following categories according to their diameter: (i) oocytes from primordial follicles: diameter <20m, (ii) oocytes from primary follicles: 25-35m, (iii) oocytes from small secondary follicles: 40-60m, (iv) oocytes from large secondary follicles: 65-85m, (v) oocytes from small antral follicles: 100-120m, and (vi) oocytes from large antral follicles: >128m. Total RNA was extracted from four pools of 25 oocytes for each category of follicles, and the genes were quantified by qPCR. Target gene expression was normalized using the gene PPIA. The results suggest that stocks of the studied transcript genes accumulate before the final phase of folliculogenesis. The HDAC2 gene was the only gene in which a differential expression was observed at stage associated with competence acquisition.
Expression regulated by
Comment
Ovarian localization
Oocyte
Comment
Segev H, et al 2001 reported the expression patterns of histone deacetylases in bovine oocytes
and early embryos, and the effect of their inhibition on embryo
development.
Gene expression at the onset of bovine embryogenesis is developmentally
regulated and histone deacetylases (HDACs) have been shown to play a key role
in the control of gene expression during this period of development. The authors determined expression pattern(s) of powerful repressors, namely
histone deacetylase-1, -2 and -3, that may in part regulate gene expression
during bovine oogenesis and early embryogenesis at the mRNA and protein
levels. Detected fragments of the hdac genes were sequenced and comparison of
the sequences showed very high homologies between DNA and amino acid sequences
of bovine HDACs and those of human and mouse.
Follicle stages
Comment
Phenotypes
Mutations
2 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: infertile - ovarian defect Comment: Compensatory functions of histone deacetylase 1 (HDAC1) and HDAC2 regulate transcription and apoptosis during mouse oocyte development. Ma P et al. Dramatic changes in chromatin structure and histone modification occur during oocyte growth, as well as a global cessation of transcription. The role of histone modifications in these processes is poorly understood. We report the effect of conditionally deleting Hdac1 and Hdac2 on oocyte development. Deleting either gene has little or no effect on oocyte development, whereas deleting both genes results in follicle development arrest at the secondary follicle stage. This developmental arrest is accompanied by substantial perturbation of the transcriptome and a global reduction in transcription even though histone acetylation is markedly increased. There is no apparent change in histone repressive marks, but there is a pronounced decrease in histone H3K4 methylation, an activating mark. The decrease in H3K4 methylation is likely a result of increased expression of Kdm5b because RNAi-mediated targeting of Kdm5b in double-mutant oocytes results in an increase in H3K4 methylation. An increase in TRP53 acetylation also occurs in mutant oocytes and may contribute to the observed increased incidence of apoptosis. Taken together, these results suggest seminal roles of acetylation of histone and nonhistone proteins in oocyte development.
Species: mouse
Mutation name: None
type: null mutation fertility: infertile - ovarian defect Comment: Histone Deacetylase 2 (HDAC2) Regulates Chromosome Segregation and Kinetochore Function via H4K16 Deacetylation during Oocyte Maturation in Mouse. Ma P et al. 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.