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1. Zhu, Qiaoqiao, 1991-. Crosstalk between long non-coding RNAs and circadian chromatin.
Degree: PhD, Circadian rhythms, 2020, Rutgers University
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.Advisors/Committee Members: Belden, William J. (chair), Anthony, Tracy G (internal member), Sarkar, Dipak (internal member), Lee, KiBum (outside member), School of Graduate Studies.
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APA (6th Edition):
Zhu, Qiaoqiao, 1. (2020). Crosstalk between long non-coding RNAs and circadian chromatin. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/64311/
Chicago Manual of Style (16th Edition):
Zhu, Qiaoqiao, 1991-. “Crosstalk between long non-coding RNAs and circadian chromatin.” 2020. Doctoral Dissertation, Rutgers University. Accessed January 18, 2021. https://rucore.libraries.rutgers.edu/rutgers-lib/64311/.
MLA Handbook (7th Edition):
Zhu, Qiaoqiao, 1991-. “Crosstalk between long non-coding RNAs and circadian chromatin.” 2020. Web. 18 Jan 2021.
Zhu, Qiaoqiao 1. Crosstalk between long non-coding RNAs and circadian chromatin. [Internet] [Doctoral dissertation]. Rutgers University; 2020. [cited 2021 Jan 18]. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/64311/.
Council of Science Editors:
Zhu, Qiaoqiao 1. Crosstalk between long non-coding RNAs and circadian chromatin. [Doctoral Dissertation]. Rutgers University; 2020. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/64311/