Alternative titles; symbols
HGNC Approved Gene Symbol: TAF4B
Cytogenetic location: 18q11.2 Genomic coordinates (GRCh38): 18:26,226,445-26,391,685 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 18q11.2 | ?Spermatogenic failure 13 | 615841 | Autosomal recessive | 3 |
TATA-binding protein-associated factors (TAFs) participate, with TATA-binding protein (TBP; 600075), in the formation of the TFIID protein complex (see 313650), which is involved in the initiation of gene transcription by RNA polymerase II (see 180660). Dikstein et al. (1996) reported that differentiated B cells contain a novel substoichiometric TAF of 105 kD not found associated with TFIID isolated from other cell types. They purified the protein (called TAFII105 by them) and cloned the human gene from a Daudi cell cDNA library using PCR primers designed from the protein sequence. The cDNA revealed a highly conserved C-terminal domain shared by TAFII130 (TAF2C) and TAFII110 as well as a divergent N-terminal coactivator domain. All cells tested expressed TAFII105 mRNA but only B cells contained significant levels of the protein in association with TFIID. These and other properties of the protein suggested to Dikstein et al. (1996) that TAFII105 is a cell type-specific subunit of TFIID that may be responsible for mediating transcription by a subset of activators in B cells. See also TAF2C1 (601796).
Gross (2020) mapped the TAF4B gene to chromosome 18q11.2 based on an alignment of the TAF4B sequence (GenBank AK302593) with the genomic sequence (GRCh38).
Using yeast 2-hybrid analysis, Gustafson et al. (2020) identified Zfp628 (610671) as a Taf4b-interacting transcriptional cofactor in mice. Endogenous Zfp628 coimmunoprecipitated with Taf4b in protein isolates from mouse testis. As with Taf4b mutants, Zfp628-deficient male mice were sterile.
In a consanguineous Turkish family in which 4 of 8 brothers were infertile due to spermatogenic failure (SPGF13; 615841), Ayhan et al. (2014) identified homozygosity for a nonsense mutation in the TAF4B gene (R611X; 601689.0001) that segregated with disease in the family and that was not found in controls.
Freiman et al. (2001) generated mice deficient in TAFII105 by targeted disruption. Female mice lacking TAFII105 are viable but infertile because of a defect in folliculogenesis correlating with restricted expression of TAFII105 in the granulosa cells of the ovarian follicle. Freiman et al. (2001) used gene expression profiling to uncover a defective inhibin-activin signaling pathway in TAFII105-deficient ovaries. Together, these studies suggested that TAFII105 mediates the transcription of a subset of genes required for proper folliculogenesis in the ovary and established TAFII105 as a cell type-specific component of the mammalian transcriptional machinery. TAFII105-deficient ovaries showed decreased expression of the following genes: inhibin beta-B (147390), aromatase p450, inhibin beta-A (147290), cyclin D2 (123833), 17-beta hydroxysteroid dehydrogenase I (109684), follistatin (136470), and inhibin-alpha (147380).
Falender et al. (2005) found that male Taf4b-null mice were initially fertile, but they became infertile by 3 months of age and eventually exhibited germ cell loss and testicular degeneration. At birth, testes of Taf4b-null males appeared histologically normal; however, at postnatal day 3, gonocyte proliferation was impaired and expression of the spermatogonial stem cell markers Ret (164761), Plzf (ZNF145; 176797), and Stra8 (609987) was reduced. Falender et al. (2005) concluded that TAF4B is required for the regulation of spermatogonial stem cell specification and proliferation in the adult.
In 4 infertile brothers from a highly consanguineous Turkish family with spermatogenic failure (SPGF13; 615841), Ayhan et al. (2014) identified homozygosity for a c.1831C-T transition in exon 9 of the TAF4B gene, causing an arg611-to-ter (R611X) substitution. The mutation was predicted to truncate 252 residues and to result in a protein lacking the histone-fold domain as well as the TAF12 (600773)-interaction domain. An unaffected brother with 9 children was heterozygous for the mutation, which was not found in 120 population controls.
Ayhan, O., Balkan, M., Guven, A., Hazan, R., Atar, M., Tok, A., Tolun, A. Truncating mutations in TAF4B and ZMYND15 causing recessive azoospermia. J. Med. Genet. 51: 239-244, 2014. [PubMed: 24431330] [Full Text: https://doi.org/10.1136/jmedgenet-2013-102102]
Dikstein, R., Zhou, S., Tjian, R. Human TAF(II)105 is a cell type-specific TFIID subunit related to hTAF(II)130. Cell 87: 137-146, 1996. [PubMed: 8858156] [Full Text: https://doi.org/10.1016/s0092-8674(00)81330-6]
Falender, A. E., Freiman, R. N., Geles, K. G., Lo, K. C., Hwang, K., Lamb, D. J., Morris, P. L., Tjian, R., Richards, J. S. Maintenance of spermatogenesis requires TAF4b, a gonad-specific subunit of TFIID. Genes Dev. 19: 794-803, 2005. [PubMed: 15774719] [Full Text: https://doi.org/10.1101/gad.1290105]
Freiman, R. N., Albright, S. R., Zheng, S., Sha, W. C., Hammer, R. E., Tjian, R. Requirement of tissue-selective TBP-associated factor TAFII105 in ovarian development. Science 293: 2084-2087, 2001. [PubMed: 11557891] [Full Text: https://doi.org/10.1126/science.1061935]
Gross, M. B. Personal Communication. Baltimore, Md. 7/2/2020.
Gustafson, E. A., Seymour, K. A., Sigrist, K., Rooij, D. G. D. E., Freiman, R. N. ZFP628 is a TAF4b-interacting transcription factor required for mouse spermiogenesis. Molec. Cell. Biol. 40: e00228-19, 2020. Note: Electronic Article. [PubMed: 31932482] [Full Text: https://doi.org/10.1128/MCB.00228-19]