报告题目：Mathematical modeling and investigating disordered chromatin interactions in cancers
Structural disorder of chromatin interactions (SDCI) is widely observed in chromosomes of cancer cells at different spatial scales and is one of the hallmarks of human cancers. The discovery of recurrent SDCIs and their molecular consequences for disrupting gene regulation and transcription is of great importance for not only understanding pathogenic mechanisms, but also providing diagnostic and prognostic information in the clinic. (1) We provide a novel and unbiased method, CAPTURE- 3C-seq, to identify locus-specific long-range DNA interactions by using the CRISPR /dCas9 system and Bayesian model analysis. In situ capture of individual constituents of the enhancer cluster controlling human β-globin genes establishes evidence for composition-based hierarchical organization. Furthermore, unbiased analysis of chromatin interactions at disease-associated cis-elements and developmentally regulated super-enhancers reveals spatial features that causally control gene transcription. (2) To systematically discover genome-wide disorders of chromatin interactions in prostate cancer, we successfully performed ChIA-PET on four prostate cancer cell lines. By building a novel mathematical model/theory for comparing the interaction signals of different cells, we discovered a large number of chromatin interactions that have significant changes in interaction strengths. Detailed analysis of these interactions revealed dramatic amplification-based regulation of the androgen receptor (AR) gene as well as the dysregulation of both KLK3 and MYC. We show that AR gene amplification is associated with the formation of new enhancers that interact with the AR promoter.
陈勇，理学博士，现任美国德克萨斯州大学达拉斯分校助理教授，曾任济南大学教师，清华大学博士后，中国科学院生物物理研究所副研究员。自2003年以来主要从事癌症系统生物学及表观遗传学研究，在Cell，Nature Protocol，PNAS，NAR，Bioinformatics 等国际顶级杂志发表论文30余篇，累积影响因子>150，累积他人学术引用>1000，主持并参加国家自然科学基金-数学天元基金，面上项目，重大研究计划项目，美国自然科学基金（NFS）等多项。