PRC1 and PRC2 proximal interactome in mouse embryonic stem cells.

IF 6.9 1区生物学 Q1 CELL BIOLOGY Cell reports Pub Date : 2025-03-25 Epub Date: 2025-03-05 DOI:10.1016/j.celrep.2025.115362

Dick W Zijlmans, Suzan Stelloo, Danique Bax, Yavor Yordanov, Pien Toebosch, Maximilian W D Raas, Sigrid Verhelst, Lieke A Lamers, Marijke P A Baltissen, Pascal W T C Jansen, Guido van Mierlo, Maarten Dhaenens, Hendrik Marks, Michiel Vermeulen

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Abstract

Polycomb repressive complexes PRC1 and PRC2 control lineage-specific gene silencing during early embryogenesis. To better understand Polycomb biology, we profile the proximal interactome (proxeome) of multiple PRC1 and PRC2 subunits in mouse embryonic stem cells (mESCs). This analysis identifies >100 proteins proximal to PRC1 and PRC2, including transcription factors and RNA-binding proteins. Notably, approximately half of the PRC2 interactors overlap with PRC1. Pluripotency-associated factors, including NANOG, colocalize with PRC2 at specific genomic sites. Following PRC2 disruption, NANOG relocalizes to other genomic regions. Interestingly, we identify PRC1 members in PRC2 proxeomes but not reciprocally. This suggests that PRC1 and PRC2 may have independent functions in addition to their cooperative roles in establishing H3K27me3-marked chromatin domains. Finally, we compare PRC2 proxeomes across different cellular contexts, including ground-state mESCs, serum-cultured mESCs, and embryoid bodies. These analyses provide a comprehensive resource, enhancing our understanding of Polycomb biology and its dynamic role across developmental states.

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小鼠胚胎干细胞中PRC1和PRC2近端相互作用组。

Polycomb抑制复合物PRC1和PRC2在早期胚胎发生中控制谱系特异性基因沉默。为了更好地理解Polycomb生物学，我们分析了小鼠胚胎干细胞（mESCs）中多个PRC1和PRC2亚基的近端相互作用组（proxeome）。该分析鉴定了靠近PRC1和PRC2的bbb100蛋白，包括转录因子和rna结合蛋白。值得注意的是，大约一半的PRC2相互作用体与PRC1重叠。包括NANOG在内的多能性相关因子与PRC2在特定基因组位点共定位。在PRC2中断后，NANOG重新定位到其他基因组区域。有趣的是，我们在PRC2邻近体中发现了PRC1成员，但不是相互的。这表明PRC1和PRC2除了在建立h3k27me3标记的染色质结构域中发挥协同作用外，还可能具有独立的功能。最后，我们比较了不同细胞背景下的PRC2邻近体，包括基态mESCs、血清培养mESCs和胚状体。这些分析提供了一个全面的资源，增强了我们对多梳生物学及其在发育状态中的动态作用的理解。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.