YEAF1/RYBP and YAF-2 are functionally distinct members of a cofactor family for the YY1 and E4TF1/hGABP transcription factors
YEAF1/RYBP and YAF-2 are functionally distinct members of a cofactor family for the YY1 and E4TF1/hGABP transcription factors
复制标题
DOI：
10.1074/jbc.m203060200
复制
发表时间：
2002-06-21
影响因子：
4.8
通讯作者：
Handa, H
中科院分区：
文献类型：
--
作者：
Sawa, C;Yoshikawa, T;Handa, H
转录因子hGABP/E4 TF 1是由两个DNA结合亚基（hGABPa/E4 TF 1 -60）和两个反式激活亚基（hGABPbeta/E4 TF 1 -53）组成的异源四聚体复合物。为了了解hGABP转录调控的分子机制，我们使用酵母双杂交筛选来寻找与非DNA结合亚基hGABP β相互作用的蛋白质。我们确定了一个人类cDNA编码的蛋白质相关的YAF-2（YY 1相关因子2），这是以前分离的相互作用伙伴的阴阳1（YY 1）转录因子。反映了这种相似性，YAF-2和这种新的蛋白质（命名为YEAF 1 YY 1和E4 TF 1/hGABP相关因子-1）与hGABPbeta和YY 1在体外和体内相互作用，表明YEAF 1和YAF-2构成了这两个结构不同的转录因子的辅因子家族。通过酵母三杂交实验，我们证明了只有在YEAF 1存在的情况下hGABPbeta和YY 1才能形成复合物，表明YEAF 1是这两个转录因子的桥接因子。这些辅因子在功能上不同，因为YAF-2正调节hGABP的转录活性，而YEAF 1负调节该活性。此外，YAF-2 mRNA在骨骼肌中高表达，而YEAF 1 mRNA在胎盘中高表达。我们推测hGABP的转录活性部分受这些组织特异性辅因子的表达水平调节。这些结果提供了一种新的转录调控机制的功能不同的辅因子家族成员。
The transcription factor hGABP/E4TF1 is a heterotetrameric complex composed of two DNA-binding subunits (hGABPalpha/E4TF1-60) and two transactivating subunits (hGABPbeta/E4TF1-53). In order to understand the molecular mechanism of transcriptional regulation by hGABP, we searched for proteins that interact with the non-DNA-binding subunit, hGABPbeta, using yeast two-hybrid screening. We identified a human cDNA encoding a protein related to YAF-2 (YY1-associated factor 2), which was previously isolated as an interacting partner of the Ying-Yang-1 (YY1) transcription factor. Reflecting this similarity, both YAF-2 and this novel protein (named YEAF1 for YY1- and E4TF1/hGABP-associated factor-1) interacted with hGABPbeta and YY1 in vitro and in vivo, indicating that YEAF1 and YAF-2 constitute a cofactor family for these two structurally distinct transcription factors. By using yeast three-hybrid assay, we demonstrated that hGABPbeta and YY1 formed a complex only in the presence of YEAF1, indicating that YEAF1 is a bridging factor of these two transcription factors. These cofactors are functionally different in that YAF-2 positively regulates the transcriptional activity of hGABP but YEAF1 negatively regulates this activity. Also, YAF-2 mRNA is highly expressed in skeletal muscle, whereas YEAF1 mRNA is highly expressed in placenta. We speculate that the transcriptional activity of hGABP is in part regulated by the expression levels of these tissue-specific cofactors. These results provide a novel mechanism of transcriptional regulation by functionally distinct cofactor family members.