| TATA-box binding protein associated factor 4b | OKDB#: 1297 |
| Symbols: | TAF4B | Species: | human | ||
| Synonyms: | SPGF13, TAF2C2, TAFII105 | Locus: | 18q11.2 in Homo sapiens |
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Entrez Gene
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| General Comment |
Transcription factor TFIID, composed of TBP and TAFII subunits, is a central component of the RNA polymerase II machinery.The first cell type-specific subunit of TFIID, called TAFII105, was identified as a polypeptide that coprecipitated with TATA-binding protein (TBP) and the other TAFIIs from a highly differentiated human B cell line but not other cell lines .
TATA-binding protein associated factors (TAFs) participate, with TATA binding protein (TBP;OMIM 600075), in the
formation of the TFIID protein complex (see TAF2A; OMIM 313650), which is involved in the initiation of gene transcription
by RNA polymerase II.
NCBI Summary: TATA binding protein (TBP) and TBP-associated factors (TAFs) participate in the formation of the TFIID protein complex, which is involved in initiation of transcription of genes by RNA polymerase II. This gene encodes a cell type-specific TAF that may be responsible for mediating transcription by a subset of activators in B cells. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2014] |
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| General function | Nucleic acid binding, DNA binding, Transcription factor | ||||
| Comment | |||||
| Cellular localization | Nuclear | ||||
| Comment | |||||
| Ovarian function | Follicle development, Initiation of primordial follicle growth, Cumulus cell differentiation, Oocyte growth, Oocyte maturation, Early embryo development | ||||
| Comment | TAF4b promotes mouse primordial follicle assembly and oocyte survival. Grive KJ 2014 et al. Primary ovarian insufficiency (POI) affects 1% of women under the age of 40 and is associated with premature ovarian follicle depletion. TAF4b deficiency in adult female mouse models results in hallmarks of POI including stereotyped gonadotropin alterations indicative of early menopause, poor oocyte quality, and infertility. However, the precise developmental mechanisms underlying these adult deficits remain unknown. Here we show that TAF4b is required for the initial establishment of the primordial follicle reserve at birth. Ovaries derived from TAF4b-deficient mice at birth exhibit delayed germ cell cyst breakdown and a significant increase in Activated Caspase 3 staining compared to control ovaries. Culturing neonatal TAF4b-deficient ovaries with the pan-caspase inhibitor ZVAD-FMK suppresses the excessive loss of these oocytes around the time of birth. These data reveal a novel TAF4b function in orchestrating the correct timing of germ cell cyst breakdown and establishment of the primordial follicle reserve during a critical window of development. ///////////////////////// Cell-type-selective induction of c-jun by TAF4b directs ovarian-specific transcription networks. Geles KG et al. Cell-type-selective expression of the TFIID subunit TAFII105 (renamed TAF4b) in the ovary is essential for proper follicle development. Although a multitude of signaling pathways required for folliculogenesis have been identified, downstream transcriptional integrators of these signals remain largely unknown. Here, we show that TAF4b controls the granulosa-cell-specific expression of the proto-oncogene c-jun, and together they regulate transcription of ovary-selective promoters. Instead of using cell-type-specific activators, our findings suggest that the coactivator TAF4b regulates the expression of tissue-specific genes, at least in part, through the cell-type-specific induction of c-jun, a ubiquitous activator. Importantly, the loss of TAF4b in ovarian granulosa cells disrupts cellular morphologies and interactions during follicle growth that likely contribute to the infertility observed in TAF4b-null female mice. These data highlight a mechanism for potentiating tissue-selective functions of the basal transcription machinery and reveal intricate networks of gene expression that orchestrate ovarian-specific functions and cell morphology. Ovarian granulosa cell survival and proliferation requires the gonad-selective TFIID subunit TAF4b. Voronina E et al. Oocyte development in the mammalian ovary requires productive interactions with somatic granulosa cells of the ovarian follicle. Proliferating granulosa cells support the progression of follicular growth and maturation, multiplying dramatically as it unfolds. The cell cycle recruitment of granulosa cells is regulated at least in part by hormones such as follicle-stimulating hormone (FSH) and estrogen. Follicles recruited into the growth phase following formation of multiple layers of granulosa cells have two major fates: either to continue proliferation followed by differentiation, or to die by programmed cell death, or atresia. While many of the signaling pathways orchestrating ovarian follicle development are known, the downstream transcriptional regulators that integrate such signals in the mammalian ovary remain to be defined. Recent experiments in diverse organisms have revealed multiple instances of gonad-selective components of the basal transcriptional machinery. One such protein, TAF4b, is a gonadal-enriched coactivator subunit of the TFIID complex required for normal female fertility in the mouse. To determine the etiology of female infertility of the TAF4b-deficient mice, we have determined multiple functions of TAF4b during postnatal ovarian follicle development. Here we demonstrate that the TAF4b protein is expressed in the granulosa cell compartment of the mammalian ovarian follicle. Furthermore, TAF4b-deficient mouse ovaries contain reduced numbers of primordial as well as growing follicles and a concomitant increased proportion of apoptotic follicles in comparison to wild type counterparts. Importantly, TAF4b-null follicles are largely resistant to induction of proliferation in response to multiple hormonal stimuli including estrogen and FSH and demonstrate compromised granulosa cell survival. Together, these data suggest that TAF4b integrates a program of granulosa cell gene expression required for normal ovarian follicle survival and proliferation in response to diverse ovarian signaling events. | ||||
| Expression regulated by | Steroids | ||||
| Comment | Estrogen-Responsiveness of the TFIID Subunit TAF4B in the Normal Mouse Ovary and in Ovarian Tumors. Wardell JR 2013 et al. Estrogen signaling in the ovary is a fundamental component of normal ovarian function and evidence also indicates that excessive estrogen is a risk factor for ovarian cancer. We have previously demonstrated that the gonadally enriched TFIID subunit TAF4B, a paralog of the general transcription factor TAF4A, is required for fertility in mice and for the proliferation of ovarian granulosa cells following hormonal stimulation. However, the relationship between TAF4B and estrogen signaling in the normal ovary or during ovarian tumor initiation and progression has yet to be defined. Here, we show that Taf4b mRNA and TAF4B protein, but not Taf4a mRNA or TAF4A protein, is increased in whole ovaries and granulosa cells of the ovary after exposure to 17beta-estradiol or the synthetic estrogen diethylstilbestrol, and that this response occurs within hours after stimulation. Further, this increase occurs via nuclear estrogen receptors (ERs), both in vivo and in a mouse granulosa cancer cell line, NT-1. We observe a significant increase of Taf4b mRNA in mouse ovarian tumors, which correlates with diminished survival of these mice. These data highlight the novel response of the general transcription factor TAF4B to estrogen in the normal ovary and during ovarian tumor progression in the mouse, suggesting its potential role in regulating actions downstream of estrogen stimulation. ///////////////////////// The TATA binding protein associated factor 4b (TAF4b) mediates FSH stimulation of the IGFBP-3 promoter in cultured porcine ovarian granulosa cells. Ongeri EM et al. We have established the gene for IGF binding protein-3 (IGFBP-3) as a target for FSH action. FSH effects on this gene require the PKA pathway as well as the PI-3 kinase and MAPK pathways. At the IGFBP-3 promoter, FSH effects depend on a site for TATA box binding protein (TBP) and formation of a high molecular weight transcription complex. To further elucidate FSH effects on the downstream events involving the TBP site, we cloned a pig TAF4b cDNA into a P-Flag expression vector. By co-transfecting granulosa cells with the IGFBP-3 promoter, we found that TAF4b mimics and enhances FSH induction of IGFBP-3 reporter activity. Using RT-PCR we showed that FSH stimulates expression of TAF4b. This would suggest that the role of TAF4b in follicular development is regulated by FSH. TAF4b may thus be the TFIID component that binds to the TBP site on the IGFBP-3 promoter and is essential for FSH induction of IGFBP-3. | ||||
| Ovarian localization | Oocyte, Granulosa | ||||
| Comment | Cyclic AMP-dependent modification of gonad-selective TAF(II)105 in a human ovarian granulosa cell line Wu Y, et al . In response to gonadotropins, the elevated level of intracellular-cyclic AMP (cAMP) in ovarian granulosa cells triggers an ordered activation of multiple ovarian genes, which in turn promotes various ovarian functions including folliculogenesis and steroidogenesis. Identification and characterization of transcription factors that control ovarian gene expression are pivotal to the understanding of the molecular basis of the tissue-specific gene regulation programs. The recent discovery of the mouse TATA binding protein (TBP)-associated factor 105 (TAF(II)105) as a gonad-selective transcriptional co-activator strongly suggests that general transcription factors such as TFIID may play a key role in regulating tissue-specific gene expression. Here we show that the human TAF(II)105 protein is preferentially expressed in ovarian granulosa cells. We also identified a novel TAF(II)105 mRNA isoform that results from alternative exon inclusion and is predicted to encode a dominant negative mutant of TAF(II)105. Following stimulation by the adenylyl cyclase activator forskolin, TAF(II)105 in granulosa cells undergoes rapid and transient phosphorylation that is dependent upon protein kinase A (PKA). Thus, our work suggests that pre-mRNA processing and post-translational modification represent two important regulatory steps for the gonad-specific functions of human TAF(II)105. | ||||
| Follicle stages | Antral | ||||
| Comment | Cell-type-selective induction of c-jun by TAF4b directs ovarian-specific transcription networks Geles KG, et al . Cell-type-selective expression of the TFIID subunit TAFII105 (renamed TAF4b) in the ovary is essential for proper follicle development. Although a multitude of signaling pathways required for folliculogenesis have been identified, downstream transcriptional integrators of these signals remain largely unknown. Here, we show that TAF4b controls the granulosa-cell-specific expression of the proto-oncogene c-jun, and together they regulate transcription of ovary-selective promoters. Instead of using cell-type-specific activators, our findings suggest that the coactivator TAF4b regulates the expression of tissue-specific genes, at least in part, through the cell-type-specific induction of c-jun, a ubiquitous activator. Importantly, the loss of TAF4b in ovarian granulosa cells disrupts cellular morphologies and interactions during follicle growth that likely contribute to the infertility observed in TAF4b-null female mice. These data highlight a mechanism for potentiating tissue-selective functions of the basal transcription machinery and reveal intricate networks of gene expression that orchestrate ovarian-specific functions and cell morphology. | ||||
| Phenotypes | |||||
| Mutations |
4 mutations
Species: mouse
Species: mouse
Species: mouse
Species: mouse
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| Genomic Region | show genomic region | ||||
| Phenotypes and GWAS | show phenotypes and GWAS | ||||
| Links |
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| created: | Sept. 16, 2001, 6:50 a.m. | by: |
hsueh email:
home page: |
| last update: | June 29, 2016, 11:31 a.m. | by: | hsueh email: |
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