Electronic Thesis and Dissertation Repository

Genomic Domains And Tissue Type Conservation Of Chromatin Accessibility Differences Between Human Metaphase Homologues

Seana L. Hill, The University of Western Ontario

Abstract

During mitosis, interphase chromatin structures change dramatically to allow formation of discrete chromosomes. The mechanisms that follow, allowing rapid and reproducible re-establishment of functional interphase organizations, remain elusive. Our laboratory identified locus-specific condensation differences (referred to as differential accessibility [DA]) in metaphase chromosome homologues by visualizing genome sequence-defined single-copy (sc) DNA probes using fluorescence in situ hybridization (FISH). Original identifications of DA loci were performed with individual scFISH probes (1.5–4kb) in lymphocyte chromosomes. In this study, we computationally designed multiple adjacent scFISH probes for 6 different DA loci and determined that DA occurs in domains. Domain lengths varied from ~16kb-130kb. DA was also investigated in other cell types (bone marrow and fibroblast samples) using 5 known DA probes and found to be maintained. DA is a conserved, structural feature in metaphase chromosomes that may play a role in the maintenance of chromosome memory from parent to daughter cells.