University of Tasmania
Browse
132086 - The association between vitamin D and multiple sclerosis.pdf (3.04 MB)

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

Download (3.04 MB)
journal contribution
posted on 2023-05-20, 02:57 authored by Lu, M, Bennet McComishBennet McComish, Kathryn BurdonKathryn Burdon, Bruce TaylorBruce Taylor, Heinrich KornerHeinrich Korner
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.

History

Publication title

Frontiers in Immunology

Volume

10

Article number

488

Number

488

Pagination

1-16

ISSN

1664-3224

Department/School

Menzies Institute for Medical Research

Publisher

Frontiers Research Foundation

Place of publication

Switzerland

Rights 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/

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified

Usage metrics

    University Of Tasmania

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC