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:
Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to the histone deacetylase/acuc/apha family. It has histone deacetylase activity and represses transcription when tethered to a promoter. It may participate in the regulation of transcription through its binding with the zinc-finger transcription factor YY1. This protein can also down-regulate p53 function and thus modulate cell growth and apoptosis. This gene is regarded as a potential tumor suppressor gene. [provided by RefSeq, Jul 2008]
General function
Cell death/survival, DNA Replication
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Cellular localization
Nuclear
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Ovarian function
Oogenesis, Oocyte maturation
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HDAC3 promotes meiotic apparatus assembly in mouse oocytes via modulating tubulin acetylation. Li X et al. (2017) Histone deacetylases (HDACs) have been shown to deacetylate numerous cellular substrates that govern a wide array of biological processes. HDAC3, a member of the Class I HDACs, is a highly conserved and ubiquitously expressed protein. However, its roles in meiotic oocytes are currently unknown. In the present study, we find that mouse oocytes depleted of HDAC3 are unable to completely progress through meiosis, blocking at metaphase I. These HDAC3-knockdown (HDAC3-KD) oocytes show spindle/chromosome organization failure, with severely impaired kinetochore-microtubule attachments. Consistent with this, the level of BubR1, a central component of the spindle assembly checkpoint, at kinetochores is dramatically increased in metaphase oocytes following HDAC3 depletion. Moreover, knockdown and overexpression experiments reveal that HDAC3 modulates the acetylation status of α-tubulin in mouse oocytes. Importantly, the deacetylation-mimetic mutant Tubulin-K40R can partly rescue the defective phenotypes of HDAC3-KD oocytes. In summary, our data support a model where HDAC3, through deacetylating tubulin, promotes the microtubule stability and establishment of kinetochore-microtubule interaction, consequently ensuring proper spindle morphology, accurate chromosome movement, and orderly meiotic progression during oocyte maturation.//////////////////
Expression regulated by
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Ovarian localization
Oocyte
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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
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Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: type: null mutation fertility: subfertile Comment: HDAC3 maintains oocyte meiosis arrest by repressing amphiregulin expression before the LH surge. Wang H et al. (2019) It is known that granulosa cells (GCs) mediate gonadotropin-induced oocyte meiosis resumption by releasing EGF-like factors in mammals, however, the detailed molecular mechanisms remain unclear. Here, we demonstrate that luteinizing hormone (LH) surge-induced histone deacetylase 3 (HDAC3) downregulation in GCs is essential for oocyte maturation. Before the LH surge, HDAC3 is highly expressed in GCs. Transcription factors, such as FOXO1, mediate recruitment of HDAC3 to the amphiregulin (Areg) promoter, which suppresses AREG expression. With the LH surge, decreased HDAC3 in GCs enables histone H3K14 acetylation and binding of the SP1 transcription factor to the Areg promoter to initiate AREG transcription and oocyte maturation. Conditional knockout of Hdac3 in granulosa cells in vivo or inhibition of HDAC3 activity in vitro promotes the maturation of oocytes independent of LH. Taking together, HDAC3 in GCs within ovarian follicles acts as a negative regulator of EGF-like growth factor expression before the LH surge.//////////////////