BACKGROUND Progesterone receptor membrane component 1 (PGRMC1) is often elevated in cancers, and exists in alternative states of phosphorylation. A motif centered on PGRMC1 Y180 was evolutionarily acquired concurrently with the embryological gastrulation organizer that orchestrates vertebrate tissue differentiation. RESULTS Here, we show that mutagenic manipulation of PGRMC1 phosphorylation alters cell metabolism, genomic stability, and CpG methylation. Each of several mutants elicited distinct patterns of genomic CpG methylation. Mutation of S57A/Y180/S181A led to increased net hypermethylation, reminiscent of embryonic stem cells. Pathways enrichment analysis suggested modulation of processes related to animal cell differentiation status and tissue identity, as well as cell cycle control and ATM/ATR DNA damage repair regulation. We detected different genomic mutation rates in culture. CONCLUSIONS A companion manuscript shows that these cell states dramatically affect protein abundances, cell and mitochondrial morphology, and glycolytic metabolism. We propose that PGRMC1 phosphorylation status modulates cellular plasticity mechanisms relevant to early embryological tissue differentiation.

中文翻译：

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PGRMC1对代谢，基因组突变和CpG甲基化的影响暗示着在动物生物学和疾病中的关键作用。

背景技术孕酮受体膜成分1（PGRMC1）在癌症中经常升高，并以磷酸化的替代状态存在。进化得到以PGRMC1 Y180为中心的基序，并与协调脊椎动物组织分化的胚胎胃形成组织器同时发生。结果在这里，我们表明PGRMC1磷酸化的诱变操纵改变细胞代谢，基因组稳定性和CpG甲基化。几个突变体中的每一个引起基因组CpG甲基化的不同模式。S57A / Y180 / S181A的突变导致净超甲基化增加，使人联想到胚胎干细胞。途径富集分析表明与动物细胞分化状态和组织身份有关的过程的调节，以及细胞周期控制和ATM / ATR DNA损伤修复调控。我们在培养物中检测到不同的基因组突变率。结论伴随手稿显示，这些细胞状态显着影响蛋白质丰度，细胞和线粒体形态以及糖酵解代谢。我们建议PGRMC1磷酸化状态调节与早期胚胎组织分化有关的细胞可塑性机制。