The determinations of nucleosome positioning.

OBJECTIVE: Nucleosomes are the basic packaging units of chromatin, determinants of nucleosome organization playing a major role in genome packaging. Although a wide variety of nucleosome organization factors have been considered separately across the whole or partial human genomic regions, it is unclarified that what the major determinants and their roles in scale are when being put all together. And it is also unknown that what the similarities and differences of determinants between different genomic features such as genes of different expression levels or genomic regions with different functions. MATERIALS AND METHODS: We detected commonalities and characteristics of nucleosome positioning determinants in different genes and regions with 1591486 nucleosomes identified by ourselves in human CD4+ cell. RESULTS: It was found that a distinct linear combination of about 20 nucleosome-positioning factors explained nucleosome occupancy for each genomic feature. In those linear combinations, 6 DNA sequence attributes (Roll stiffness and Twist stiffness, CT and AG, CG and shift stiffness) and a histone modification (H4R3me2) are shared. And other factors are varied. Roll stiffness and Twist stiffness are the most important features. They are dominant, alone explaining 96.61-98.45% of the positioning weight in each genomic feature. The characteristic factors in each combination are larger in number, but weaker in power. Numerous histone modifications play a subtle role for nucleosome positioning. CONCLUSIONS: The present study provides a more accurate positioning nucleosome-map with higher resolution and a dramatically simplified means to predict and understand intrinsic nucleosome occupancy in different genomic features in human CD4+ cell. Roll stiffness and Twist stiffness are the two most important determinants in all genomic features. They may dominate because they both determine the degree of DNA bending and correlates with many other DNA structural characteristics. Histone modifications play a role of subtle allocation for nucleosome occupancy.