Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC, Australia.
EMBL-Australia, Clayton, VIC, Australia.
Nucleic Acids Res. 2022 May 20;50(9):4813-4839. doi: 10.1093/nar/gkac290.
Polycomb group proteins predominantly exist in polycomb repressive complexes (PRCs) that cooperate to maintain the repressed state of thousands of cell-type-specific genes. Targeting PRCs to the correct sites in chromatin is essential for their function. However, the mechanisms by which PRCs are recruited to their target genes in mammals are multifactorial and complex. Here we review DNA binding by polycomb group proteins. There is strong evidence that the DNA-binding subunits of PRCs and their DNA-binding activities are required for chromatin binding and CpG targeting in cells. In vitro, CpG-specific binding was observed for truncated proteins externally to the context of their PRCs. Yet, the mere DNA sequence cannot fully explain the subset of CpG islands that are targeted by PRCs in any given cell type. At this time we find very little structural and biophysical evidence to support a model where sequence-specific DNA-binding activity is required or sufficient for the targeting of CpG-dinucleotide sequences by polycomb group proteins while they are within the context of their respective PRCs, either PRC1 or PRC2. We discuss the current knowledge and open questions on how the DNA-binding activities of polycomb group proteins facilitate the targeting of PRCs to chromatin.
多梳蛋白主要存在于多梳抑制复合物（PRC）中，这些复合物合作维持数千个细胞类型特异性基因的抑制状态。将 PRC 靶向染色质中的正确位点对于其功能至关重要。然而，在哺乳动物中，PRC 被募集到其靶基因的机制是多因素和复杂的。在这里，我们回顾多梳蛋白的 DNA 结合。有强有力的证据表明，PRC 的 DNA 结合亚基及其 DNA 结合活性对于细胞中染色质结合和 CpG 靶向是必需的。在体外，观察到截断蛋白在其 PRC 之外的上下文之外对 CpG 特异性结合。然而，仅仅是 DNA 序列并不能完全解释在任何给定细胞类型中 PRC 靶向的 CpG 岛的子集。此时，我们发现很少有结构和生物物理证据支持这样一种模型，即序列特异性 DNA 结合活性对于多梳蛋白在其各自的 PRC（PRC1 或 PRC2）内靶向 CpG-二核苷酸序列是必需的或充分的。我们讨论了目前关于多梳蛋白的 DNA 结合活性如何促进 PRC 靶向染色质的知识和悬而未决的问题。
