The University of Texas MD Anderson Cancer Center, Science Park-Research Division, P.O. Box 389, Smithville, TX 78957, USA.
Mol Cell. 2010 Dec 22;40(6):1016-23. doi: 10.1016/j.molcel.2010.11.024.
Specific sites of histone tail methylation are associated with transcriptional activity at gene loci. These methyl marks are interpreted by effector molecules, which harbor protein domains that bind the methylated motifs and facilitate either active or inactive states of transcription. CARM1 and PRMT1 are transcriptional coactivators that deposit H3R17me2a and H4R3me2a marks, respectively. We used a protein domain microarray approach to identify the Tudor domain-containing protein TDRD3 as a "reader" of these marks. Importantly, TDRD3 itself is a transcriptional coactivator. This coactivator activity requires an intact Tudor domain. TDRD3 is recruited to an estrogen-responsive element in a CARM1-dependent manner. Furthermore, ChIP-seq analysis of TDRD3 reveals that it is predominantly localized to transcriptional start sites. Thus, TDRD3 is an effector molecule that promotes transcription by binding methylarginine marks on histone tails.
组蛋白尾部甲基化的特定位点与基因座的转录活性有关。这些甲基标记被效应分子所解释，这些效应分子具有结合甲基化基序的蛋白结构域，从而促进转录的活跃或不活跃状态。CARM1 和 PRMT1 是转录共激活因子，分别沉积 H3R17me2a 和 H4R3me2a 标记。我们使用蛋白质结构域微阵列方法鉴定出含有 Tudor 结构域的蛋白 TDRD3 是这些标记的“读取器”。重要的是，TDRD3 本身就是一个转录共激活因子。这种共激活因子活性需要完整的 Tudor 结构域。TDRD3 以 CARM1 依赖的方式被募集到雌激素反应元件。此外，对 TDRD3 的 ChIP-seq 分析表明，它主要定位于转录起始位点。因此，TDRD3 是一种效应分子，通过结合组蛋白尾部的甲基精氨酸标记来促进转录。
