Department of Animal Biology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104, USA and College of Science Health and Liberal Arts, Philadelphia University, 4201 Henry Avenue, Philadelphia, PA 19144, USA.
Nucleic Acids Res. 2014 Feb;42(4):2208-23. doi: 10.1093/nar/gkt1187. Epub 2013 Nov 26.
Polycomb Group (PcG) proteins are crucial for epigenetic inheritance of cell identity and are functionally conserved from Drosophila to humans. PcG proteins regulate expression of homeotic genes and are essential for axial body patterning during development. Earlier we showed that transcription factor YY1 functions as a PcG protein. YY1 also physically interacts with YAF2, a homolog of RYBP. Here we characterize the mechanism and physiologic relevance of this interaction. We found phenotypic and biochemical correction of dRYBP mutant flies by mouse YAF2 demonstrating functional conservation across species. Further biochemical analysis revealed that YAF2 bridges interaction between YY1 and the PRC1 complex. ChIP assays in HeLa cells showed that YAF2 is responsible for PcG recruitment to DNA, which is mediated by YY1 DNA binding. Knock-down of YY1 abrogated PcG recruitment, which was not compensated by exogenous YAF2 demonstrating that YY1 DNA binding is a priori necessary for Polycomb assembly on chromatin. Finally, we found that although YAF2 and RYBP regulate a similar number of Polycomb target genes, there are very few genes that are regulated by both implying functional distinction between the two proteins. We present a model of YAF2-dependent and independent PcG DNA recruitment by YY1.
多梳抑制复合物（PcG）蛋白对于细胞身份的表观遗传遗传至关重要，并且从果蝇到人类在功能上是保守的。PcG 蛋白调节同源基因的表达，并且对于发育过程中的轴向身体模式形成是必需的。我们之前表明，转录因子 YY1 作为 PcG 蛋白发挥作用。YY1 还与 RYBP 的同源物 YAF2 发生物理相互作用。在这里，我们描述了这种相互作用的机制和生理相关性。我们发现通过小鼠 YAF2 对 dRYBP 突变体苍蝇进行表型和生化校正，证明了物种间的功能保守性。进一步的生化分析表明，YAF2 桥接了 YY1 和 PRC1 复合物之间的相互作用。HeLa 细胞中的 ChIP 测定表明，YAF2 负责 PcG 向 DNA 的募集，这是由 YY1 DNA 结合介导的。YY1 的敲低消除了 PcG 的募集，而外源性 YAF2 并不能补偿，这表明 YY1 DNA 结合对于多梳在染色质上的组装是必要的。最后，我们发现尽管 YAF2 和 RYBP 调节相似数量的 PcG 靶基因，但仅有极少数基因受两者共同调控，这意味着这两种蛋白之间存在功能区别。我们提出了一种由 YY1 依赖和独立的 YAF2 进行 PcG DNA 募集的模型。
