TAF8 explained

Transcription initiation factor TFIID subunit 8 is a protein that in humans is encoded by the TAF8 gene.^[1]

This gene encodes one of several TATA-binding protein (TBP)-associated factors (TAFs), which are integral subunits of the general transcription factor complex TFIID. TFIID recognizes the core promoter of many genes and nucleates the assembly of a transcription preinitiation complex containing RNA polymerase II and other initiation factors. The protein encoded by this gene contains an H4-like histone fold domain, and interacts with several subunits of TFIID including TBP and the histone-fold protein TAF10. Alternatively spliced transcript variants have been described, but their biological validity has not been determined.

Clinical significance

Mutations of the TAF8 gene cause a neurodegenerative disorder first described in 2022^[2] and presenting as severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy.

Further reading

• Zhou Q, Sharp PA . Novel mechanism and factor for regulation by HIV-1 Tat . EMBO J. . 14 . 2 . 321–8 . 1995 . 7835343 . 10.1002/j.1460-2075.1995.tb07006.x. 398086 .
• Parada CA, Yoon JB, Roeder RG . A novel LBP-1-mediated restriction of HIV-1 transcription at the level of elongation in vitro . J. Biol. Chem. . 270 . 5 . 2274–83 . 1995 . 7836461 . 10.1074/jbc.270.5.2274 . free .
• Richard Gaynor . Ou SH, Garcia-Martínez LF, Paulssen EJ, Gaynor RB . Role of flanking E box motifs in human immunodeficiency virus type 1 TATA element function . J. Virol. . 68 . 11 . 7188–99 . 1994 . 7933101 . 10.1128/JVI.68.11.7188-7199.1994. 237158 .
• Kashanchi F . Direct interaction of human TFIID with the HIV-1 transactivator tat . Nature . 367 . 6460 . 295–9 . 1994 . 8121496 . 10.1038/367295a0 . vanc. Piras G . Radonovich MF . 3 . Duvall . Janet F. . Fattaey . Ali . Chiang . Cheng-Ming . Roeder . Robert G. . Brady . John N. . 1994Natur.367..295K . 4362048 .
• Wang Z . Wild-type and transactivation-defective mutants of human immunodeficiency virus type 1 Tat protein bind human TATA-binding protein in vitro . J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. . 12 . 2 . 128–38 . 1996 . 8680883 . 10.1097/00042560-199606010-00005 . vanc. Morris GF . Rice AP . 3 . Xiong . W . Morris . CB . free.
• Pendergrast PS, Morrison D, Tansey WP, Hernandez N . Mutations in the carboxy-terminal domain of TBP affect the synthesis of human immunodeficiency virus type 1 full-length and short transcripts similarly . J. Virol. . 70 . 8 . 5025–34 . 1996 . 8764009 . 10.1128/JVI.70.8.5025-5034.1996. 190456 .
• Kashanchi F . Interaction of human immunodeficiency virus type 1 Tat with a unique site of TFIID inhibits negative cofactor Dr1 and stabilizes the TFIID-TFIIA complex . J. Virol. . 70 . 8 . 5503–10 . 1996 . 8764062 . 10.1128/JVI.70.8.5503-5510.1996. 190508 . vanc. Khleif SN . Duvall JF . 3 . Sadaie . MR . Radonovich . MF . Cho . M . Martin . MA . Chen . SY . Weinmann . R .
• Zhou Q, Sharp PA . Tat-SF1: cofactor for stimulation of transcriptional elongation by HIV-1 Tat . Science . 274 . 5287 . 605–10 . 1996 . 8849451 . 10.1126/science.274.5287.605 . 1996Sci...274..605Z . 13266489 .
• García-Martínez LF, Ivanov D, Gaynor RB . Association of Tat with purified HIV-1 and HIV-2 transcription preinitiation complexes . J. Biol. Chem. . 272 . 11 . 6951–8 . 1997 . 9054383 . 10.1074/jbc.272.11.6951 . free .
• Purrello M . Genomics and transcription analysis of human TFIID . Oncogene . 16 . 12 . 1633–8 . 1998 . 9569032 . 10.1038/sj.onc.1201673 . vanc. Di Pietro C . Viola A . 3 . Rapisarda . Antonella . Stevens . Sean . Guermah . Mohamed . Tao . Yong . Bonaiuto . Corrada . Arcidiacono . Antonio . free .
• Guermah M, Tao Y, Roeder RG . Positive and Negative TAFII Functions That Suggest a Dynamic TFIID Structure and Elicit Synergy with TRAPs in Activator-Induced Transcription . Mol. Cell. Biol. . 21 . 20 . 6882–94 . 2001 . 11564872 . 10.1128/MCB.21.20.6882-6894.2001 . 99865 .
• Tora L . A unified nomenclature for TATA box binding protein (TBP)-associated factors (TAFs) involved in RNA polymerase II transcription . Genes Dev. . 16 . 6 . 673–5 . 2002 . 11963920 . 10.1101/gad.976402 . free .
• Strausberg RL . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . vanc. Feingold EA . Grouse LH . 3 . Derge . JG . Klausner . RD . Collins . FS . Wagner . L . Shenmen . CM . Schuler . GD . 2002PNAS...9916899M . free .
• Guermah M, Ge K, Chiang CM, Roeder RG . The TBN protein, which is essential for early embryonic mouse development, is an inducible TAFII implicated in adipogenesis . Mol. Cell . 12 . 4 . 991–1001 . 2003 . 14580349 . 10.1016/S1097-2765(03)00396-4 . free .
• Ota T . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . vanc. Suzuki Y . Nishikawa T . 3 . Otsuki . Tetsuji . Sugiyama . Tomoyasu . Irie . Ryotaro . Wakamatsu . Ai . Hayashi . Koji . Sato . Hiroyuki . free .
• Soutoglou E . The Nuclear Import of TAF10 Is Regulated by One of Its Three Histone Fold Domain-Containing Interaction Partners . Mol. Cell. Biol. . 25 . 10 . 4092–104 . 2005 . 15870280 . 10.1128/MCB.25.10.4092-4104.2005 . 1087738 . vanc. Demény MA . Scheer E . 3 . Fienga . G. . Sassone-Corsi . P. . Tora . L. .

Notes and References

1. Web site: Entrez Gene: TBN taube nuss homolog (mouse).
2. Wong KM, Jepsen WM, Efthymiou S, Salpietro V, Sanchez-Castillo M, Yip J, Kriouile Y, Diegmann S, Dreha-Kulaczewski S, Altmüller J, Thiele H, Nürnberg P, Toosi MB, Akhondian J, Ghayoor Karimiani E, Hummel-Abmeier H, Huppke B, Houlden H, Gärtner J, Maroofian R, Huppke P . Mutations in TAF8 cause a neurodegenerative disorder . Brain: A Journal of Neurology . 145. 9. 3022–3034. June 2022 . 35759269 . 10.1093/brain/awac154 . free .