Nuclear receptor function requires a TFTC-type histone acetyl transferase complex.
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.
Yanagisawa
Junn
J
Institute of Molecular and Cellular Biosciences, Graduate School of Agricultural and Life Sciences, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Kitagawa
Hirochika
H
Yanagida
Mitsuaki
M
Wada
Osamu
O
Ogawa
Satoko
S
Nakagomi
Madoka
M
Oishi
Hajime
H
Yamamoto
Yasuji
Y
Nagasawa
Hiromich
H
McMahon
Steven B
SB
Cole
Michael D
MD
Tora
Laszlo
L
Takahashi
Nobuhiro
N
Kato
Shigeaki
S
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
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