LanguageTerm (authority = ISO 639-3:2007); (type = text)
English
Abstract (type = abstract)
The circadian rhythm is governed by transcriptional negative feedback facilitated by oscillating histone modifications and chromatin remodeling. The circadian rhythm is entrained by external zeitgebers (light and temperature) and are conserved in Neurospora, Drosophila, zebrafish, and mammals. The clock gene frequency in Neurospora and Period2 in vertebrates have natural antisense transcripts (NATs) whose function is not understood. In this dissertation I examined the connection among the circadian clock, non-coding RNAs and heterochromatin formation on both on the genome-wide and locus-specific level using a multi-organism approach. I performed a genome-wide study, using RNA-seq and ChIP-seq to understand the role of H3 lysine 4 methyltransferase (KMT2/SET-1) and histone H3 lysine 9 methyltransferase (KMT1/DIM-5) in Neurospora to understand the role of 2 seemingly opposing modifications. Integrated analysis of RNA-seq and ChIP-seq showed crosstalk and redistributions between histone H3 lysine 4 tri-methylation (H3K4me3) and histone H3 lysine 9 tri-methylation (H3K9me3). I also examined how perturbing the expression of a diurnal lncRNA affected downstream heterochromatin formation at the telomeres. The core circadian clock controls rhythms in TERRA, a long noncoding RNA that originates from telomeres and my research shows alcohol disrupts the diurnal rhythm in TERRA and heterochromatin at the telomere, which in theory makes telomeres more susceptible to DNA damage. I also examined the Per2 NAT, Per2AS and found the diurnal rhythm in Per2AS is dependent on BMAL1. Using the ChIRP-MS, I identified Per2AS-interacting proteins. Specifically, I found hnRNP M interacts with Per2AS and hnRNP M is required to maintain the normal amplitude and period of Per2. Furthermore, I demonstrate that hnRNP M is necessary for H3K9me3 and H3K27me3 at Per2. These findings support a model where Per2AS may serve as scaffold for hnRNP M and other associated proteins that assist in heterochromatin formation at Per2. Collectively, this dissertation furthers our understanding of the circadian clock, non-coding RNAs, and circadian regulated facultative heterochromatin formation.
Subject (authority = LCSH)
Topic
Circadian rhythms
Subject (authority = LCSH)
Topic
Ribonucleases
Subject (authority = RUETD)
Topic
Endocrinology and Animal Biosciences
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.