Nucleosome Positioning Effects on Cell-type Specificity and Gene Regulation in the Drosophila melanogaster Genome

Public Deposited

In eukaryotic organisms, genomic DNA is organized and condensed into repeating arrays of nucleosomes. The histone protein octamer of each nucleosome wraps 147 base pairs of DNA, effectively restricting access by transcription factors and other regulatory proteins to that region. An additional histone, histone H1, binds the DNA outside the core octamer and may influence nucleosome positioning. Studies in yeast reveal that the overwhelming majority of nucleosome positions are encoded in the genome by specific signals that favor or disfavor nucleosome occupancy. The extent to which this is also true in multicellular eukaryotes has been questioned and is not presently known. My research seeks to help resolve this ambiguity by exploring the relationship between nucleosome positions, higher order chromatin fiber structure, and gene regulation in Drosophila melanogaster. I created high-resolution genome wide nucleosome maps from Drosophila cell lines to probe key aspects of chromatin structure. By analyzing nucleosome occupancy between discrete cell lines I show differences in nucleosome occupancy over specific motifs that may help to define the final cell fate. Furthermore, I examine the role of the non-canonical linker histone, Histone H1, in Drosophila chromatin through genome-wide maps of H1 generated using chromatin immunoprecipitation/parallel DNA sequencing (ChIP-Seq) methods. Data from this map suggest dynamic and mutually exclusive binding of H1 and the chromatin architectural protein, HMGD1, to modulate the local chromatin state. The results presented in this thesis contribute high-resolution data to the library of information available on nucleosome organization in eukaryotes. These data provide a framework to further study the interplay between chromatin architecture and epigenetic gene regulation

Last modified
  • 04/18/2018
Date created
Resource type
Rights statement