Chromatin globules: a common motif of higher order chromosome structure?

Recent technological advances in the field of chromosome conformation capture are facilitating tremendous progress in the ability to map the three-dimensional (3D) organization of chromosomes at a resolution of several Kb and at the scale of complete genomes. Here we review progress in analyzing chromosome organization in human cells by building 3D models of chromatin based on comprehensive chromatin interaction datasets. We describe recent experiments that suggest that long-range interactions between active functional elements are sufficient to drive folding of local chromatin domains into compact globular states. We propose that chromatin globules are commonly formed along chromosomes, in a cell type specific pattern, as a result of frequent long-range interactions among active genes and nearby regulatory elements. Further, we speculate that increasingly longer range interactions can drive aggregation of groups of globular domains. This process would yield a compartmentalized chromosome conformation, consistent with recent observations obtained with genome-wide chromatin interaction mapping.     

染色质互作相关转录因子的挖掘及功能分析

染色质互作是真核生物基因组组装的基础,并且在调控真核基因细胞特异性表达中发挥重要作用.染色质互作的发生与特定的蛋白质有关,目前已经发现CTCF (CCCTC binding facor,转录阻抑物)和黏连蛋白与染色质互作相关,然而并不清楚是否还有其他蛋白质参与染色质互作.我们将整合高通量染色体构象捕获(Hi-C)和染色质免疫沉淀-测序(ChIP-seq)数据,在GM12878和K562细胞系中挖掘与染色质互作相关的转录因子,并对发现的转录因子做功能分析.我们在频繁发生互作的染色质位点中发现RUNX3、SPI1等转录因子也可能参与染色质互作.另外,通过FP-growth的数据挖掘方法还发现多个转录因子可能协同作用参与染色质互作.研究结果将为染色质互作相关实验的开展提供先验知识.