11月5日 Understanding the epigenome through specialized regulatory DNA elements


 
报告人:周巨民 教授
主持人:黄静 副教授
时 间:11月5日 13:30 - 14:30
地 点:中山北路校区理科大楼B307
 
报告人简介:
  周巨民博士1982年进入上海复旦大学,1986年获生物学学士学位并获“上海市高校优秀毕业生”称号。1986年秋进入中国科学院上海药物研究所。1989年进入美国德克萨斯大学M.D. Anderson癌症医学中心埃里克。奥尔森(Eric Olson)实验室学习,于1995年获生物化学博士学位。从1995至2000年,在加利福尼亚大学伯克利分校(Mike Levine博士实验室)从事博士后研究。现任威斯达研究所(Wistar Institute)副教授,美国宾夕法尼亚大学医学院遗传学院兼职教授。
  周巨民博士已在《细胞》(Cell),《分子细胞》(Molecular Cell), 《基因和发育》(Gene and Development), PNAS,Development,Developmental Biology, and Journal of Virology 等顶级期刊上发表多篇学术论文。总影响因子超过200。
 
报告内容简介:
  Homeotic genes in the Hox cluster determine the body plan during development and maintain identities of cell through out adult life. Mutations in these genes lead to developmental defects, cancer and other diseases. These genes are arranged in clusters and are highly conserved during evolution. We are interested in the mechanisms that regulated the Drosophila homeotic genes complex, the bithorax complex (BXC). My previous and studies in my laboratory have identified several chromatin boundaries from the Abd-B domain of BXC. We, together with studies from other groups, found that these boundaries genetically organize the regulatory region of Abd-B into tissue specific chromatin domains of 15-25 kb each. We found that each of these domain boundary interact with a zinc finger DNA binding insulator protein called CTCF. We conducted a genome wide study of the binding sites for CTCF and found that CTCF also regulate many other developmentally important genes.
  Because CTCF insulators also block the activity of enhancers, having CTCF insulators within the regulatory regions would pose problems for the Abd-B locus. To solve this paradox, we identified a novel type of DNA element called Promoter Targeting Sequence (PTS). We found that the PTS can overcome the enhancer blocking effect of insulators, thus allow enhancers to activate the Abd-B promoter over insulator elements. The PTS exhibit a range of distinct properties that ensure specific enhancer-promoter interaction over long distances. Most importantly, the PTS carries an epigenetically determined pattern of promoter activation and transmit the pattern through the germ line. This non-Mendelian inheritance highlights the importance of proper wiring of the regulatory network in the Hox cluster.
  In addition to our studies of insulators in the fly genome, we are also interested in the chromatin in human diseases. Currently, we are working on the human Herpes Simplex virus (HSV). We are interested in the role of CTCF in viral DNA replication, gene expression and latency establishment. We found that two CTCF insulators flanking the latency specific transcript LAT, the only transcribed region in the genome during latency. These elements may serve to protect the LAT, from neighboring heterochromatin.
  Finally, I will discuss our current research project and lay out our future plans to study human disease epigenome.
 
生命科学学院
2010年11月4日