A Quantitative Analysis Of The Impact On Chromatin Accessibility By Histone Modifications And Binding Of Transcription Factors

DNase I hypersensitive sites are regions in chromatin that aresupersensitive to the cleavage of DNase I. These regions are predominantlyfound in many active genes and cis-regulatory elements. Traditionally, theyare viewed as open chromatin and play important roles in many biologicalprocesses, including transcription, replication, and differentiation. It hasbeen shown that chromatin features such as histone modifications and thebinding of transcription factors exert a significant impact on the “openness”of chromatin.In this study, we present a quantitative analysis of the genome-widerelationship between chromatin features and chromatin accessibility inDNase I hypersensitive sites. We found that these features show distinctpreference to localize in open chromatin. In order to elucidate the exact impact, we derived quantitative models to directly predict the “openness” ofchromatin using histone modification features and transcription factorbinding features, respectively. We show that these two types of features arehighly predictive for chromatin accessibility in a statistical viewpoint.Moreover, our results indicate that these features are highly redundant andonly a small number of features are needed to achieve a very high predictivepower.Our study provides new insights into the true biological phenomenaand the combinatorial effects of chromatin features to differential DNase Ihypersensitivity. It also gives some directions of further studies in this field.