The Structure and Function of Chromatin and Chromosomes

Abstract

BackgroundOne of the striking features of the eukaryotic nucleus is that chromosomes adopt preferred conformations that vary across different tissues and developmental stages. Many lines of evidence suggest the functional significance of genome architecture, including the existence of chromosomes territories [1], the correlation between radial positioning of chromosomes with gene density, transcriptional activity, replication timing and chromosome size [2][3][4][5], the tissue-specific spatial configurations of chromosomes relative to one another [6,7], the co-localization of disparate DNA elements into functionally defined aggregates or "factories" [9][10][11][12][13], and the predisposition to human disease, including cancer by predisposition to acquisition of karyotypic defects [14][15][16][17]. Collectively, these various lines of evidence indicate an intimate relationship between genome structure and function. These findings also emphasize the need to characterize both local and global chromosome structure to understand the underlying regulatory mechanisms of various genome functions.In broad terms, three types of molecular biology tools are currently available to characterize chromosome structure. 3C and its derivatives are now the most commonly used tools for characterizing chromosome structure [24][25][26][27][28][29][30][31][32][33][34]. During the past two years, three 3C-based methods have been developed to identify chromatin interactions genome-wide, revealing the folding principles of the human genome [35] and enabling the construction of 3D models of the genomes of haploid budding yeast [36] and fission yeast [37]. The regulation of eukaryotic gene expression depends on transcription factors and cofactors acting on functional DNA elements such as promoters, enhancers, silencers and insulators, which are situated in a three-dimensional space. While systematic efforts such as those of the NIH