Chromosomal Interaction in Chromatin Organization

Genes are arranged linearly in long DNA strands. Genomic DNA must be packaged tightly to be contained in the nucleus. Studies have shown that chromosomes are folded in an ordered three-dimensional organization for nuclear packaging. How chromatin organization is regulated and related to gene expression are fundamental cell biological and genetic issues. Chromosome folding occurs through specific protein-protein and protein-DNA interactions. Such interactions are involved in the long-range regulation of enhancer and silencer activities for transcriptional control. This chapter discusses molecular technologies for mapping genome-wide long-range chromosomal interactions. Hi-CHi-C is introduced as a powerful method of identifying chromatin interactions in the entire genome. Analysis of mammalian genomes reveals that chromosomes are organized in topologically associated domainstopologically associated domain (TADsTAD). The relationship between TAD domains, epigenetic status, and transcriptional activity is an important topic to be discussed. The organization of TAD domains is remarkably conserved in human and mouse embryonic stemembryonic stem cells. Some insulators are highly enriched at the TAD boundariesTAD boundary, implying their roles in transcriptional insulationinsulation at the boundaries. Gene expression profiles change during development of cell-type specification and differentiation. We will examine whether TAD structures are also modified during differentiation. Evolutionary conservation and differences between mammalian and insect TADs are also discussed.