Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; Faculty of Sciences, University of Basel, 4056 Basel, Switzerland.
Mol Cell. 2015 Apr 2;58(1):157-71. doi: 10.1016/j.molcel.2015.02.013. Epub 2015 Mar 19.
Polycomb repressive complexes PRC1 and PRC2 regulate expression of genes involved in proliferation and development. In mouse early embryos, however, canonical PRC1 localizes to paternal pericentric heterochromatin (pat-PCH), where it represses transcription of major satellite repeats. In contrast, maternal PCH (mat-PCH) is enriched for H3 lysine 9 tri-methylation (H3K9me3) and Hp1β. How PRC1 is targeted to pat-PCH, yet excluded from mat-PCH, has remained elusive. Here, we identify a PRC1 targeting mechanism that relies on Cbx2 and Hp1β. Cbx2 directs catalytically active PRC1 to PCH via its chromodomain (CD(Cbx2)) and neighboring AT-hook (AT(Cbx2)) binding to H3K27me3 and AT-rich major satellites, respectively. CD(Cbx2) prevents AT(Cbx2) from interacting with DNA at PCH marked by H3K9me3 and Hp1β. Loss-of-function studies show that Hp1β and not H3K9me3 prevents PRC1 targeting to mat-PCH. Our findings indicate that CD(Cbx2) and AT(Cbx2) separated by a short linker function together to integrate H3K9me3/HP1 and H3K27me3 states.
多梳抑制复合物 PRC1 和 PRC2 调节参与增殖和发育的基因的表达。然而，在小鼠早期胚胎中，典型的 PRC1 定位于父本着丝粒异染色质（pat-PCH），在那里它抑制主要卫星重复序列的转录。相比之下，母本 PCH（mat-PCH）富含 H3 赖氨酸 9 三甲基化（H3K9me3）和 Hp1β。PRC1 如何靶向 pat-PCH，而又不靶向 mat-PCH，一直难以捉摸。在这里，我们确定了一种依赖于 Cbx2 和 Hp1β 的 PRC1 靶向机制。Cbx2 通过其 chromodomain（CD(Cbx2)) 和邻近的 AT-hook（AT(Cbx2)) 分别与 H3K27me3 和富含 AT 的主要卫星结合，将催化活性的 PRC1 靶向 PCH。CD(Cbx2) 防止 AT(Cbx2)与 H3K9me3 和 Hp1β 标记的 PCH 上的 DNA 相互作用。功能丧失研究表明，是 Hp1β 而不是 H3K9me3 阻止了 PRC1 靶向 mat-PCH。我们的研究结果表明，由短接头分隔的 CD(Cbx2) 和 AT(Cbx2) 共同整合 H3K9me3/HP1 和 H3K27me3 状态。
