title: Nuclear receptor function requires a TFTC-type histone acetyl transferase complex.
abstract: Nuclear receptors (NRs) regulate transcription in a ligand-dependent way through two types of coactivator complexes: the p160/CBP histone acetyl transferase (HAT) complex and the DRIP/TRAP/SMCC complex without HAT activity. Here we identified a large human (h) coactivator complex necessary for the estrogen receptor alpha (ERalpha) transactivation. This complex contains the GCN5 HAT, the c-Myc interacting protein TRRAP/PAF400, TAF(II)30, and other subunits. Similarly to known TFTC (TBP-free TAF(II)-containing)-type HAT complexes (hTFTC, hPCAF, and hSTAGA), TRRP directly interacted with liganded ER alpha, or other NRs. ER alpha transactivation was enhanced by the purified complex in vitro. Antisense TRRAP RNA inhibited estrogen-dependent cell growth of breast cancer cells. Thus, the isolated TFTC-type HAT complex acts as a third class of coactivator complex for NR function.
authors.affiliation: Institute of Molecular and Cellular Biosciences, Graduate School of Agricultural and Life Sciences, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Junn
authors.initials: J
authors.lastname: Yanagisawa
authors.forename: Hirochika
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Yanagida
authors.forename: Osamu
authors.initials: O
authors.lastname: Wada
authors.forename: Satoko
authors.initials: S
authors.lastname: Ogawa
authors.forename: Madoka
authors.initials: M
authors.lastname: Nakagomi
authors.forename: Hajime
authors.initials: H
authors.lastname: Oishi
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Hiromich
authors.initials: H
authors.lastname: Nagasawa
authors.forename: Steven B
authors.initials: SB
authors.lastname: McMahon
authors.forename: Michael D
authors.initials: MD
authors.lastname: Cole
authors.forename: Laszlo
authors.initials: L
authors.lastname: Tora
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Takahashi
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D018797:Cell Cycle Proteins; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D047628:Estrogen Receptor alpha; D051548:Histone Acetyltransferases; D006801:Humans; D008024:Ligands; D046911:Macromolecular Substances; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000235:genetics*; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
chemical_list: D000123:Acetyltransferases; D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D047628:Estrogen Receptor alpha; D051548:Histone Acetyltransferases; D008024:Ligands; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D016372:RNA, Antisense; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C113829:transformation-transcription domain-associated protein; C501179:KAT2A protein, human; C496553:KAT7 protein, human