The packing of mammalian chromosome: a phase transition perspective
Spatial organization of DNA into chromosomes, which can be characterized by cell-specific interactions between local or long range segments, is thought to contribute to controlling and regulating essential nuclear functions in cells, but is only partially understood. In this talk, we describe a multi-scale approach that has been applied to understand this problem. Using molecular dynamics simulations we showed that DNA structure can be significantly affected by epigenetic modifications such as DNA methylation, the distribution of which shows disease (e.g., cancer)-dependent scale-invariant behavior in various biological samples. We then utilized Hi-C data to construct models for autosomes of different types of human cells and show that the epigenetic markers are strongly related to the 3-D chromosome structure. The high-order structure of chromosome is thus thought to be strongly affected by the DNA sequence. The distribution of dinucleotides along the linear genome also shows a power-law behavior, which can be explained by the multi-scale clustering of dinucleotides and the human genome can be viewed roughly as a A-B block co-polymer. We try to make a connection of such a property of genome to the higher-order chromosome structure formation, including topologically associated domains (TADs) and compartments. Finally, we will discuss the tissue-specific organization of the chromosome structure in differentiation, development, and disease, in which segregation/mixing of DNA segments of different properties characterized by CGI (CpG islands) distribution and transcription factor binding play important roles.
高毅勤，北京大学化学与分子工程学院教授，北京大学BIOPIC研究员。1993年本科毕业于四川大学化学系，1996年在中科院化学所获得硕士学位， 2001年获得加州理工学院博士学位，导师为Rudolph A. Marcus教授。2001年－2004年间在加州理工学院和哈佛大学做博士后研究（导师为Marcus和Martin Karplus教授）。2005年-2009年，美国得克萨斯农工大学化学系助理教授。2010-今，北京大学化学与分子工程学院教授。曾获Pople Medal, CMOA Prize，日本化学会Keynote Lecturer奖，美国Searle Scholar，Dreyfus新教授奖和Clauser Prize等。目前担任ACS Central Science, Chemistry of Materials, Journal of Chemical Physics，Chemical Physics Letters, Interdisciplinary Sciences, 物理化学学报等期刊编委。