转录增强子在调控基因转录和肿瘤发生过程中发挥关键作用。细胞内活跃的转录增强子被组蛋白H3K27ac和H3K4me1所标记，可以通过表观遗传组学的方法进行研究和预测。但是目前在各种癌症中关于组蛋白修饰的研究尚缺乏系统性的工作。本项目计划在乳腺癌小鼠模型中，系统性研究小鼠正常乳腺组织和乳腺癌组织的组蛋白修饰的差异，结合基于质谱的蛋白质组学技术和基于ChIP-Seq的表观遗传组学技术解析多个组蛋白修饰在肿瘤发生发展过程中在染色质上的变化规律和分子调控机制。前期实验已经发现乳腺癌中H3K27ac等修饰显著上升，表观遗传组学研究结果表明这两种修饰在转录增强子上的分布高度相关；同时我们已经鉴定出一系列在乳腺癌小鼠模型中活化的增强子，为后续研究奠定了基础。本项目的实施将为乳腺癌表观遗传组学的研究提供新思路和新靶点。

The transcription enhancers are critical for the regulation of gene expression and tumorigenesis. The active enhancers in the cells are marked with H3K27ac and H3K4me1, which can be studied and predicted with epigenomics approaches. But the systematic studies of cancer epigenomics are still not much. The current study is going to systematically study histone modifications of normal and tumor tissues in a breast cancer mouse model, by combining mass spec based proteomic technique and ChIP-Seq based epigenomic technique, and to illustrate the function of dynamic histone modifications on chromatin. Our early experiments have found that H3K27ac significantly increase in tumor tissue and the epigenomic study showed they are highly associated on transcriptional enhancers. Moreover, we have also identified a series of enhancers specific in breast tumor, supporting strongly for future studies. This project will provide novel strategy and targets for the epigenomic studies in breast cancer.