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Epigenetic Regulation of the ILK1 Promoter and its Role in Chronic Alcohol Use

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title
Epigenetic Regulation of the ILK1 Promoter and its Role in Chronic Alcohol Use
author
Bodie, Jessica
abstract
Alcohol use disorder (AUD) is a prevalent mental health condition affecting individuals globally, characterized by the inability to control alcohol consumption despite negative consequences. This disorder poses various health and societal risks incurring in $249 billion cost each year. Despite this, AUD treatments are scarce, and have limited efficacy. Epigenetic signatures in the brain have been linked to addiction disorders such as AUD. Our group previously identified a differentially methylated region upstream of the integrin-linked kinase (ILK) transcription start site in the prefrontal cortex of rhesus macaques following chronic ethanol intake. In addition, ILK was downregulated in drinking subjects. Thus, alcohol may mediate alterations in ILK activity through regulation of epigenetic signatures mapping to its promoter. ILK mediates interactions between the extracellular matrix and intracellular signaling. In the brain, it is involved in synaptic plasticity and growth factor signaling, while its inhibition is linked to addiction1,2. The goal of this research was to determine if regions of the differentially methylated region possess promoter activity and if recruitment of transcriptional activators and epigenetic modifications to these regions can alter ILK expression. In parallel, an in vivo assay will determine the efficacy of an ILK agonist in reducing ethanol intake in mice.
subject
Alcohol
CRISPR
Epigenetics
guide RNA
Integrin-linked kinase (ILK)
transcriptional activation
contributor
Cervera-Juanes, Rita P (advisor)
Hawkins, Greg A (committee member)
Appt, Susan E (committee member)
Chen, Rong (committee member)
Solberg-Woods, Leah (committee member)
date
2024-05-23T08:36:23Z (accessioned)
2024 (issued)
degree
Biomedical Science – MS (discipline)
embargo
2029-05-18 (terms)
2029-05-18 (liftdate)
identifier
http://hdl.handle.net/10339/109451 (uri)
language
en (iso)
publisher
Wake Forest University
type
Thesis

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