Mengus G, May M, Carré L, Chambon P, Davidson I
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Universite Louis Pasteur (CNRS/INSERM/ULP), Collège de France, Illkirch.
Genes Dev. 1997 Jun 1;11(11):1381-95. doi: 10.1101/gad.11.11.1381.
We report for the first time the cloning of a complete cDNA encoding the human TFIID subunit hTAF(II)135 (hTAF(II)130). Full-length hTAF(II)135 comprises 1083 amino acids and contains two conserved domains present also in dTAF(II)110 and hTAF(II)105. We show that expression of hTAF(II)135 in mammalian cells strongly and selectively potentiates transcriptional stimulation by the activation function-2 (AF-2) of the retinoic acid, thyroid hormone, and vitamin D3 receptors (RAR, TR, and VDR), but does not affect the AF-2s of the estrogen (ER) or retinoid X (RXR) receptors. The coactivator activity requires an hTAF(II)135 region that is located between the conserved domains but is itself not conserved in dTAF(II)110 and hTAF(II)105. Expression of hTAF(II)135 also stimulates RAR AF-2 activity when a promoter with a low-affinity TATA element (TGTA) is used, indicating that hTAF(II)135 overexpression compensates for the low-affinity of TBP for this promoter and may facilitate the recruitment of TFIID by the RAR AF-2.
我们首次报道了编码人TFIID亚基hTAF(II)135(hTAF(II)130)的完整cDNA的克隆。全长hTAF(II)135由1083个氨基酸组成,包含两个在dTAF(II)110和hTAF(II)105中也存在的保守结构域。我们发现,hTAF(II)135在哺乳动物细胞中的表达强烈且选择性地增强了视黄酸、甲状腺激素和维生素D3受体(RAR、TR和VDR)的激活功能-2(AF-2)的转录刺激作用,但不影响雌激素(ER)或类视黄醇X(RXR)受体的AF-2。共激活因子活性需要hTAF(II)135位于保守结构域之间的一个区域,而该区域本身在dTAF(II)110和hTAF(II)105中并不保守。当使用具有低亲和力TATA元件(TGTA)的启动子时,hTAF(II)135的表达也会刺激RAR AF-2活性,这表明hTAF(II)135的过表达补偿了TBP对该启动子的低亲和力,并可能促进RAR AF-2对TFIID的招募。