A quantitative study of nucleosome free regions in yeast by segmental semi-Markov Model using tiling microarrays

Wei Xie
M.S., 2008
Advisor: Ker-Chau Li
DNA, the fundamental molecule carrying the genetic information, is packed into the form of chromatin inside the nuclei of cells in a highly organized manner. Nucleosomes as the basic unit of chromatin are not uniformly distributed along the chromosomes and many genomic loci are depleted of nucleosomes. Nucleo-some free regions (NFRs) play an important role in many biological processes including gene regulation. As the resolution of tiling array gets higher, we expect to extract out more and more subtle quantitative properties about NFRs such as the lengths and the degree of nucleosome depletion. Because these quantities are likely to vary from one NFR to another NFR, a genome-wide portrait of each individual NFR may help shed light on the dynamic aspect of chromatin restructuring and gene regulation. Although previous studies have examined the consensus pattern of nucleosome depletion in promoter regions by a curve averaging method, the quantitative characterization of each individual NFR, despite the importance, is lost because of averaging. In this study, we presented a nucleosome occupancy data of the whole yeast genome at 4-bp resolution and developed an efficient algorithm to identify each individual “quantitative NFR” at the whole genome scale. Our result showed that the ma jority of the NFRs are located in intergenic regions/promoters with length of about 400-600 bps, which is approximately the length of DNA wrapping around two-to-three nucleosomes plus linkers. Our quantitative NFR results enable an investigation of the relative impacts of transcription machinery and DNA sequence in evicting histones from NFRs. We showed that while both factors have significant overall effects, the specific contributions vary across different subtypes of NFRs. The emphasis of our approach on the variation rather than the consensus of NFR sets the tone for enabling the exploration of many subtler dynamic aspects of chromatin biology.
2008