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Ovarian Kaleidoscope Database (OKdb)

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SET domain bifurcated 2 OKDB#: 4385
 Symbols: SETDB2 Species: human
 Synonyms: CLLD8, CLLL8, KMT1F, C13orf4  Locus: 13q14 in Homo sapiens


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General Comment NCBI Summary: This gene encodes a member of a family of proteins that contain a methyl-CpG-binding domain (MBD) and a SET domain and function as histone methyltransferases. This protein is recruited to heterochromatin and plays a role in the regulation of chromosome segregation. This region is commonly deleted in chronic lymphocytic leukemia. Naturally-occuring readthrough transcription occurs from this gene to the downstream PHF11 (PHD finger protein 11) gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]
General function Chromosome organization
Comment
Cellular localization Nuclear
Comment
Ovarian function Ovulation, Germ cell development
Comment Identification and Expression of Potential Regulators of the Mammalian Mitotic-to-Meiotic Transition. Hogarth CA et al. Meiosis is unique to germ cells and occurs in a sex-specific manner. The genes regulating meiotic initiation in either sex are yet to be fully elucidated. Recent studies have revealed the importance of retinoic acid and one of its target genes, Stra8, in meiotic initiation in both sexes. Microarray analysis of whole murine embryonic ovary and postnatal testis time course data revealed a single peak of Stra8 expression in each organ at the onset of meiosis; at E14.5 in the ovary and 10 dpp in the testis. In order to identify other genes involved in the initiation of meiosis in mammals, murine testis and ovary microarray data were examined more closely for transcripts with expression profiles similar to Stra8. Three such candidates include establishment of cohesion 1 homolog 2 (Esco2), encoding a protein essential for sister chromatid cohesion, SET domain, bifurcated 2 (Setdb2), the mouse ortholog of Eggless which is essential for oogenesis in Drosophila, and ubiquitin activating enzyme 6 (Uba6), a gene with fivefold higher expression in human and mouse testes than any other organ. In situ hybridization and immunohistochemistry or immunofluorescence were performed to localize Esco2, Setbd2 and Uba6 expression in the developing testis. The cellular expression pattern localized all three of these transcripts and their respective proteins to germ cells transitioning from mitosis to meiosis, hence supporting the hypothesis of their involvement in the initiation of meiosis. Future research will be directed at determining a specific role for these three proteins in germ cell differentiation.
Expression regulated by LH
Comment Changes in gene expression of histone modification enzymes in rat granulosa cells undergoing luteinization during ovulation. Maekawa R et al. (2016) The ovulatory LH surge rapidly alters the expression of steroidogenesis-related genes such as steroidogenic acute regulatory protein (StAR) in granulosa cells (GCs) undergoing luteinization. We recently reported that histone modifications contribute to these changes. Histone modifications are regulated by a variety of histone modification enzymes. This study investigated the changes in gene expression of histone modification enzymes in rat GCs undergoing luteinization after the induction of ovulation. The extracellular regulated kinase (ERK)-1/2 is a mediator in the intracellular signaling pathway stimulated by the ovulatory LH surge and regulates the expression of a number of genes in GCs. We further investigated whether ERK-1/2 is involved in the regulation of the histone modification at the StAR promoter region in GCs undergoing luteinization. GCs were obtained from rats treated with equine chorionic gonadotropin (CG) before (0 h) and after human (h) CG injection. The expressions of 84 genes regulating histone modifications or DNA methylation were measured using a PCR array. Five genes (HDAC4, HDAC10, EZH2, SETDB2, and CIITA) were identified as histone acetylation- or histone methylation-related genes, and were significantly altered after hCG injection. None of the genes were related to DNA methylation. mRNA levels of EZH2, SETDB2, HDAC4, and HDAC10 decreased and CIITA mRNA levels increased 4 or 12 h after hCG injection. GCs isolated after eCG injection were incubated with hCG for 4 h to induce luteinization. StAR mRNA levels were significantly increased by hCG accompanied by the increase in H3K4me3 of the StAR promoter region. StAR mRNA expression was inhibited by the ERK inhibitor with the significant decrease of H3K4me3. These results suggest that hCG increases StAR gene expression through the ERK-1/2-mediated signaling which is also associated with histone modification of the promoter region. Gene expressions of histone modification enzymes change in GCs undergoing luteinization after ovulation induction. This change may play important roles in regulating the expression of various genes during the early stage of luteinization, which may be critical for the subsequent corpus luteum formation.//////////////////
Ovarian localization Primordial Germ Cell, Granulosa
Comment
Follicle stages
Comment
Phenotypes
Mutations 1 mutations

Species: D. melanogaster
Mutation name: None
type: naturally occurring
fertility: infertile - ovarian defect
Comment: Eggless analog in vertebrates

Genomic Region show genomic region
Phenotypes and GWAS show phenotypes and GWAS
Links
OMIM (Online Mendelian Inheritance in Man: an excellent source of general gene description and genetic information.)
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created: Sept. 15, 2010, 10:58 a.m. by: hsueh   email:
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last update: March 22, 2016, 10:17 a.m. by: hsueh    email:



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