Induction of Histone H3K27 Methylation by Non-native Telomere Repeats in Neurospora crassa
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Date
2020
Authors
Painter, Peregrine Daniel
Journal Title
Journal ISSN
Volume Title
Publisher
University of Oregon
Abstract
To live and grow, our bodies require carefully regulated patterns of gene expression to meet the demands of our current developmental state and environment. One way our body accomplishes this regulation is through chromatin modification. Of particular interest to this paper is the methylation of lysine 27 on histone H3 (H3K27me). The di-/trimethylation of H3K27 (H3K27me2/3) is a known contributor to gene silencing and is deposited by Polycomb Repressive Complex 2 (PRC2), a complex found in some form in most eukaryotic organisms. If H3K27me is not patterned appropriately, developmental errors and disease can occur. The factors governing recruitment and activation of PRC2 remain largely unknown and understanding how the body regulates PRC2 is integral to developing treatments for the diseases featuring aberrant PRC2 activity. Telomeres are long stretches of short repeated sequences, (TTAGGG)n in vertebrates and Neurospora crassa, that protect the ends of DNA during replication. It has been shown that telomere repeats are able to induce subtelomeric H3K27me2/3 at their native locations and ectopic H3K27me2/3 if inserted internally into the genome of the fungus N. crassa, a relatively simple eukaryotic organism that sports PRC2. In this study I sought to characterize what feature of the telomeric DNA sequence is responsible for the induction of de novo H3K27me2/3. I suspected the ability of telomeres to form G-quadruplex (G4) as a likely mechanism. I designed DNA constructs featuring non-native telomere repeats and inserted them at the csr-1 locus of N. crassa. My results suggest that the ability to form G4 structure is not alone sufficient for internal repeats to induce ectopic H3K27me2/3.
Description
41 pages
Keywords
Biochemistry, Epigenetics, Chromatin, n. crassa, PRC2, Telomre, H3K27me