School of Science and Health, Philadelphia University, Schoolhouse Lane and Henry Avenue, Philadelphia, Pennsylvania 19144, USA.
J Cell Biochem. 2010 Feb 15;109(3):478-86. doi: 10.1002/jcb.22424.
The Polycomb Group (PcG) complex of transcriptional repressors is critical for the maintenance of stage-specific developmental gene expression, stem cell maintenance and for large-scale chromosomal dynamics. Functional deficiency of a single PcG gene can severely compromise PcG function, leading to developmental defects, embryonic lethality, or a number of malignancies. Despite the critical nature of PcG proteins, the mechanisms by which these complexes mediate their effects are relatively uncharacterized. Nearly all vertebrate PcG proteins lack inherent DNA binding capacity, making it unclear how they are targeted to Polycomb response element (PRE) sequences. Transcription factor YY1 is a functional ortholog of a Drosophila PcG protein, Pleiohomeotic (PHO), one of the few PcG proteins with specific DNA binding capability, and YY1 can recruit PcG proteins to specific DNA sequences. A small 25 amino acid YY1 domain (the REPO domain) is necessary and sufficient for recruitment of PcG proteins to DNA and for transcriptional repression. We show here that the YY1 REPO domain interacts with PcG protein Yaf2 and recruits Yaf2 to DNA. Interaction is lost when the YY1 REPO domain is deleted. In addition we show that Yaf2, when linked to a heterologous DNA binding domain, can recruit PcG proteins to DNA leading to transcriptional repression. When the Drosophila homolog of Yaf2 (dRYBP) is mutated, PcG recruitment to DNA is reduced. Taken together, our results suggest that Yaf2 serves as a molecular bridge between YY1 and other PcG complex proteins.
多梳抑制复合物（PcG）是转录抑制因子，对于维持特定发育阶段的基因表达、干细胞维持以及大规模染色体动力学至关重要。单个 PcG 基因的功能缺陷会严重影响 PcG 功能，导致发育缺陷、胚胎致死或多种恶性肿瘤。尽管 PcG 蛋白具有关键性作用，但这些复合物介导其效应的机制尚不清楚。几乎所有的脊椎动物 PcG 蛋白都缺乏固有 DNA 结合能力，这使得它们如何被靶向到多梳反应元件（PRE）序列变得不清楚。转录因子 YY1 是果蝇 PcG 蛋白 Pleiohomeotic（PHO）的功能同源物，PHO 是少数具有特定 DNA 结合能力的 PcG 蛋白之一，YY1 可以将 PcG 蛋白募集到特定的 DNA 序列。一个 25 个氨基酸的小 YY1 结构域（REPO 结构域）对于募集 PcG 蛋白到 DNA 和转录抑制是必需且充分的。我们在这里表明，YY1 REPO 结构域与 PcG 蛋白 Yaf2 相互作用，并将 Yaf2 募集到 DNA 上。当 YY1 REPO 结构域缺失时，相互作用就会丢失。此外，我们还表明，当 Yaf2 与异源 DNA 结合结构域相连时，它可以将 PcG 蛋白募集到 DNA 上，从而导致转录抑制。当果蝇 Yaf2 的同源物（dRYBP）发生突变时，PcG 蛋白向 DNA 的募集就会减少。综上所述，我们的结果表明，Yaf2 充当了 YY1 和其他 PcG 复合物蛋白之间的分子桥梁。
