Chromatin landscape of the "dark matter of the genome": centromeres of S. cerevisiae and repeat sequences of D. melanogaster.

Thesis (Ph.D.)--University of Washington, 2014The chromatin landscape plays a major role in defining cell phenotypes through transcriptional regulation and specification of the main features of chromosome, such as centromeres and pericentric heterochromatin. Studies of the chromatin landscape so far have been mostly confined to the protein-coding part of the genome. In this work I present a study of the chromatin landscape of two non-coding regions: centromeres in budding yeast Saccharomyces cerevisiae and pericentric repeat sequences of the fruit fly Drosophila melanogaster. I have shown that the centromere of budding yeast contains a nucleosome with a special structure, called a hemisome. This finding eliminated other previously proposed models of the centromeric nucleosome and reconciled previous conflicting observations. I also developed a method to quantify enrichment of repeat sequences in Chip-Seq experiments and used it to construct an epigenetic map of heterochromatin in D. melanogaster using public datasets Drosophila Genetic Reference Panel (DGRP) and modENCODE. This analysis yielded several unexpected biologically interesting findings such as preferential association of HP1a protein with transposable elements and depletion of nucleosomes from AT-rich short repeats sequences