The Role of DNA Methylation in Transcription Factor Activity

虽然众所周知，基因表达与DNA甲基化密切相关，但它在调节DNA结合蛋白活性方面的作用尚不清楚。最近的研究表明，Krüppel样转录因子(KLF)对甲基化的DNA序列有明显的结合偏好。该项目旨在通过定义对结合至关重要的全基因组范围的一组位点和结构域来研究转录因子的活性如何依赖于甲基化DNA的靶向。它还将通过研究DNA甲基化在KLF介导的细胞重编程到多能性状态中的重要性的方法来探索这些序列的功能意义。

Although it is well established that gene expression is closely correlated with DNA methylation, its role in regulating the activity of DNA-binding proteins remains unclear. It has recently been shown that Krüppel-like transcription factors (KLF) have distinct binding preferences for methylated DNA sequences. This project aims to investigate how the activity of transcription factors is dependent upon targeting of methylated DNA by defining the genome-wide set of sites and structural domains critical for binding. It also will explore the functional significance of these sequences using assays that investigate the importance of DNA methylation in KLF mediated cellular reprogramming to the pluripotent state.