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Multiple Sclerosis and Vitamin D Receptor super enhancers – March 2019

The Association Between Vitamin D and Multiple Sclerosis Risk: 1,25(OH)2D3 Induces Super-Enhancers Bound by VDR.

Front Immunol. 2019 Mar 19;10:488. doi: 10.3389/fimmu.2019.00488. eCollection 2019.
Lu M1,2, McComish BJ1, Burdon KP1, Taylor BV1, Körner H1,3.

VitaminDWiki

The founder of VitaminDWiki does not know what Super-enhancers are
Items in both categories MS and VDR are listed here:

Items in both categories MS and Genetics are listed here:


Press Release for the study

NEW GENETIC LINKS WITH VITAMIN D DISCOVERED IN MS

  • "They identified five MS risk genes that were strongly regulated by vitamin D super-enhancers, that is cells either made far more or less of these genes when vitamin D was present. These genes were involved in a range of functions, including immune response and inflammation in the brain. "
  • "The team also specifically investigated a particular gene called ZMIZ1 to see if it was controlled by vitamin D super-enhancers. ZMIZ1 is already of interest in MS as it has previously been shown that cells in people with MS produce a very different level of this gene compared to people without MS. The researchers found that the ZMIZ1 gene was regulated by vitamin D super-enhancers."

 Download the PDF from VitaminDWiki

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.

Created by admin. Last Modification: Tuesday October 22, 2019 18:48:11 GMT-0000 by admin. (Version 5)
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