The variant Polycomb Repressor Complex 1 component PCGF1 interacts with a pluripotency sub-network that includes DPPA4, a regulator of embryogenesis.
The variant Polycomb Repressor Complex 1 component PCGF1 interacts with a pluripotency sub-network that includes DPPA4, a regulator of embryogenesis.
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DOI：
10.1038/srep18388
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发表时间：
2015-12-21
影响因子：
4.6
通讯作者：
Cagney G
中科院分区：
文献类型：
--
作者：
Oliviero G;Munawar N;Watson A;Streubel G;Manning G;Bardwell V;Bracken AP;Cagney G
PCGF1编码与转录抑制和发育基因调控相关的六个人类Polycomb无名指同源物之一。单个PCGF蛋白定义了具有不同亚基组成的离散多梳抑制物复合体1(PRC1)，其功能尚不完全清楚。PCGF1是一个变异的PRC1复合体的组成部分，该复合体还包含BCL6共抑制子BCOR和组蛋白去甲基酶Kdm2b。为了进一步研究PCGF1的作用，我们在神经元分化的细胞模型中绘制了内源性条件下蛋白质的物理相互作用图。使用严格的统计截断法，鉴定出83个高度浓缩的相互作用蛋白，包括所有先前报道的含有PCGF1的变异PRC1复合体的成员，以及与不同细胞途径有关的蛋白质，如染色质和细胞周期调节。值得注意的是，在随后的一轮物理相互作用图谱实验中，与建立和维持多能性相关的蛋白质子网络(NANOG、OCT4、PATZ1和发育调节因子DPPA4)被发现独立地与PCGF1相互作用。此外，PCGF1的敲除导致DPPA4和变异的PRC1复合体的其他亚单位在mRNA和蛋白质水平上的表达减少。因此，PCGF1代表了Polycomb功能和多能性之间的物理和功能联系。
PCGF1 encodes one of six human Polycomb RING finger homologs that are linked to transcriptional repression and developmental gene regulation. Individual PCGF proteins define discrete Polycomb Repressor Complex 1 (PRC1) multi-protein complexes with diverse subunit composition whose functions are incompletely understood. PCGF1 is a component of a variant PRC1 complex that also contains the BCL6 co-repressor BCOR and the histone demethylase KDM2B. To further investigate the role of PCGF1, we mapped the physical interactions of the protein under endogenous conditions in a cell model of neuronal differentiation. Using stringent statistical cut-offs, 83 highly enriched interacting proteins were identified, including all previously reported members of the variant PRC1 complex containing PCGF1, as well as proteins linked to diverse cellular pathways such as chromatin and cell cycle regulation. Notably, a sub-network of proteins associated with the establishment and maintenance of pluripotency (NANOG, OCT4, PATZ1, and the developmental regulator DPPA4) were found to independently interact with PCGF1 in a subsequent round of physical interaction mapping experiments. Furthermore, knockdown of PCGF1 results in reduced expression of DPPA4 and other subunits of the variant PRC1 complex at both mRNA and protein levels. Thus, PCGF1 represents a physical and functional link between Polycomb function and pluripotency.