Plath Kathrin, Talbot Dale, Hamer Karien M, Otte Arie P, Yang Thomas P, Jaenisch Rudolf, Panning Barbara
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
J Cell Biol. 2004 Dec 20;167(6):1025-35. doi: 10.1083/jcb.200409026. Epub 2004 Dec 13.
Polycomb group (PcG) proteins belonging to the polycomb (Pc) repressive complexes 1 and 2 (PRC1 and PRC2) maintain homeotic gene silencing. In Drosophila, PRC2 methylates histone H3 on lysine 27, and this epigenetic mark facilitates recruitment of PRC1. Mouse PRC2 (mPRC2) has been implicated in X inactivation, as mPRC2 proteins transiently accumulate on the inactive X chromosome (Xi) at the onset of X inactivation to methylate histone H3 lysine 27 (H3-K27). In this study, we demonstrate that mPRC1 proteins localize to the Xi, and that different mPRC1 proteins accumulate on the Xi during initiation and maintenance of X inactivation in embryonic cells. The Xi accumulation of mPRC1 proteins requires Xist RNA and is not solely regulated by the presence of H3-K27 methylation, as not all cells that exhibit this epigenetic mark on the Xi show Xi enrichment of mPRC1 proteins. Our results implicate mPRC1 in X inactivation and suggest that the regulated assembly of PcG protein complexes on the Xi contributes to this multistep process.
属于多梳抑制复合体1和2(PRC1和PRC2)的多梳蛋白组(PcG)蛋白维持同源异型基因沉默。在果蝇中,PRC2使组蛋白H3的赖氨酸27发生甲基化,这种表观遗传标记有助于PRC1的募集。小鼠PRC2(mPRC2)与X染色体失活有关,因为在X染色体失活开始时,mPRC2蛋白会短暂积累在失活的X染色体(Xi)上,使组蛋白H3赖氨酸27(H3-K27)甲基化。在本研究中,我们证明mPRC1蛋白定位于Xi,并且在胚胎细胞X染色体失活的起始和维持过程中,不同的mPRC1蛋白在Xi上积累。mPRC1蛋白在Xi上的积累需要Xist RNA,并且不完全受H3-K27甲基化的调控,因为并非所有在Xi上表现出这种表观遗传标记的细胞都显示mPRC1蛋白在Xi上富集。我们的结果表明mPRC1参与X染色体失活,并表明PcG蛋白复合体在Xi上的有序组装有助于这一多步骤过程。