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The association between vitamin D and multiple sclerosis risk: 1,25(OH)2D3 induces super-enhancers bound by VDR

Citation

Lu, M and McComish, BJ and Burdon, KP and Taylor, BV and Korner, H, The association between vitamin D and multiple sclerosis risk: 1,25(OH)2D3 induces super-enhancers bound by VDR, Frontiers in Immunology, 10 Article 488. ISSN 1664-3224 (2019) [Refereed Article]


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Copyright Statement

Copyright 2019 Lu, McComish, Burdon, Taylor and Korner. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.3389/fimmu.2019.00488

Abstract

A super-enhancer (SE) is a cluster of enhancers with a relatively high density of particular chromatin features. SEs typically regulate key genes that can determine cell identity and differentiation. Identifying SEs and their effects may be critical in predicting key regulatory genes, such as master transcription factor genes or oncogenes. Signal inducible SEs are dense stretches of signal terminal transcription factor (TF) binding regions, and may modulate the interaction between environmental factors (e.g., Vitamin D) and genetic factors (i.e., risk variants) in complex diseases such as multiple sclerosis (MS). As a complex autoimmune disease, the etiology and progression of MS, including the interaction between Vitamin D and MS risk variants, is still unclear and can be explored from the aspect of signal SEs. Vitamin D [with its active form: 1,25(OH)2D3], is an environmental risk factor for MS. It binds the Vitamin D receptor (VDR) and regulates gene expression. This study explores the association between VDR super-enhancers (VSEs) and MS risk variants. Firstly, we reanalyse public ChIP-seq and RNA-seq data to classify VSEs into three categories according to their combinations of persistent and secondary VDR binding. Secondly, we indicate the genes with VSE regions that are near MS risk variants. Furthermore, we find that MS risk variants are enriched in VSE regions, and we indicate some genes with a VSE overlapping MS risk variant for further exploration. We also find two clusters of genes from the set of genes showing correlation of expression patterns with the MS risk gene ZMIZ1 that appear to be regulated by VSEs in THP-1 cells. It is the first time that VSEs have been analyzed, and we directly connect the genetic risk factors for MS risk with Vitamin D based on VSEs.

Item Details

Item Type:Refereed Article
Keywords:vitamin D, vitamin D receptor, inducible super-enhancer, risk allele, multiple sclerosis
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Central Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
UTAS Author:Lu, M (Mr Ming Lu)
UTAS Author:McComish, BJ (Dr Bennet McComish)
UTAS Author:Burdon, KP (Professor Kathryn Burdon)
UTAS Author:Taylor, BV (Professor Bruce Taylor)
UTAS Author:Korner, H (Professor Heinrich Korner)
ID Code:132086
Year Published:2019
Deposited By:Menzies Institute for Medical Research
Deposited On:2019-04-18
Last Modified:2019-05-03
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