Histone H3K4 methylation In hippocampal memory formation and In Alzheimer’s disease
department or school: Medicine, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Obayashi, Yuka
issued: 2021-08-19T19:43:41Z
issued: 2021
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Regulation of chromatin structure through posttranslational histone modifications is implicated in the induction of synaptic plasticity and memory formation. One such modification – histone H3 lysine 4 methylation (H3K4me) – has recently emerged as a key epigenetic modification necessary for consolidation of hippocampus-dependent memory. It is well-established that H3K4me levels across the genome are dynamically regulated by opposing activity of lysine methyltransferases (KMTs) and lysine demethylases (KDMs). They link dysregulation of H3K4 KMTs to neurodegenerative disorders, such as Alzheimer’s disease (AD). The major group of H3K4 KMTs in mammals are the Trithorax Group (TrxG) complexes, which can promote gene expression via distinct enzymatic (methylation of H3K4) and non-enzymatic (e.g. recruitment of other co-activators) mechanisms. In my project, I targeted the catalytic activity of TrxG complex and demonstrated that the loss of H3K4 methylation in mature hippocampal neurons leads to several intellectual abnormalities, such as the development of anxiety-like behaviour, recognition memory deficit, and impaired reversal memory with normal locomotory coordination in mice. Furthermore, I provided evidence of reduced H3K4 methylation in the hippocampus of AD by using a combination of patient samples and rodent disease model. Collectively, these results suggest that TrxG-mediated H3K4 methylation is required for a proper formation of hippocampal memory and may help shed light on H3K4 methylation as a novel therapeutic target for the treatment and prevention of AD.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/79343
note: HISTONE H3K4 METHYLATION IN HIPPOCAMPAL MEMORY FORMATION AND IN ALZHEIMER’S DISEASE by Yuka Obayashi B.Sc.(Hon), Simon Fraser University, 2015 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE AND POSTDOCTORIAL STUDIES (CELLL AND DEVELOPMENTAL BIOLOGY) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) August 2021 © Yuka Obayashi, 2021 iiThe following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the thesis entitled: Histone H3K4 Methylation In Hippocampal Memory Formation And In Alzheimer’s Disease submitted by Yuka Obayashi in partial fulfillment of the requirements for the degree of Master of Science in Cell and Developmental Biology Examining Committee: Dr. Bradford Hoffman, Cell and Developmental Biology Supervisor Dr. Shernaz Bamji, Cell and Developmental Biology Supervisory Committee Member Dr. Jason Snyder, Psychology Supervisory Committee Member Dr. Timothy O’Connor, Cellular and Physiological Sciences Additional Examiner Dr. Cal Roskelley, Cell and Developmental Biology Additional Examiner iiiAbstract Regulation of chromatin structure through posttranslational histone modifications is implicated in the induction of synaptic plasticity and memory formation. One such modification – histone H3 lysine 4 methylation (H3K4me) – has recently emerged as a key epigenetic modification necessary for consolidation of hippocampus-dependent memory. It is well-established that H3K4me levels across the genome are dynamically regulated by opposing activity of lysine methyltransferases (KMTs) and lysine demethylases (KDMs). They link dysregulation of H3K4 KMTs to neurodegenerative disorders, such as Alzheimer’s disease (AD). The major group of H3K4 KMTs in mammals are the Trithorax Group (TrxG) complexes, which can promote gene expression via distinct enzymatic (methylation of H3K4) and non-enzymatic (e.g. recruitment of other c…
has type: Thesis/Dissertation
date issued: 2021-11
is shown at: 10.14288/1.0401445
language: eng
degree discipline: Cell and Developmental Biology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Hoffman, Bradford Glenn
type: Text
identifier URI: http://hdl.handle.net/2429/79343