Role of SOX2 O-GIcNAcylation in pluripotency

 描述（由申请人提供）：转录因子是建立细胞类型特异性基因表达模式的核心，这些基因表达模式表征发育和成年哺乳动物中数百种不同细胞类型中的每一种。转录因子通常受到信号通路的调节，信号通路影响这些因子的活性并确保对发育和环境线索的适当转录反应。我们的初步研究表明，胚胎干细胞自我更新的核心转录因子SOX 2被修饰， 通过将O-连接的N-乙酰葡糖胺糖添加到丝氨酸残基248和苏氨酸残基213。这种修饰是由酶OGT介导的，OGT是检测葡萄糖和其他营养素水平的营养素传感途径中的核心参与者。我们建议研究SOX 2的这种翻译后修饰在自我更新中的作用，以更好地了解代谢途径如何影响多能细胞中的基因表达。

 DESCRIPTION (provided by applicant): Transcription factors are central for establishing the cell type-specific gene expression patterns that characterize each of the hundreds of different cell types in developing and adult mammals. Transcription factors are often regulated by signaling pathways, which affect the activity of these factors and ensure appropriate transcriptional responses to developmental and environmental cues. Our preliminary studies indicate that a transcription factor central to embryonic stem cell self-renewal, SOX2, is modified by addition of an O-linked N-acetylglucosamine sugar to serine residue 248 and threonine residue 213. This modification is mediated by the enzyme OGT, which is a central player in the nutrient sensing pathway that detects levels of glucose and other nutrients. We propose to investigate the role of this post-translational modification of SOX2 in self-renewal, to better understand how metabolic pathways impact gene expression in pluripotent cells.