# Search for Potential VDR/Partner Composite Elements in Regulatory DNA of Genes Associated with Respiratory Infections and Atopic Diseases

## TL;DR

This study explores how vitamin D might influence immune genes by identifying new VDR partner complexes linked to atopic diseases and respiratory infections.

## Contribution

The paper introduces novel VDR/Partner composite elements (CEs) in immune gene regulation, expanding beyond known VDR/RXRA CEs.

## Key findings

- Predicted novel VDR/NR2C2 and VDR/PPARG CEs in immune system gene regulatory regions.
- Found potential synergism between VDR/NR2C2 and VDR/RXRA CEs for the IRF5 gene.
- Observed potential synergism between VDR/PPARG and VDR/RXRA CEs for the MAPK13 gene.

## Abstract

Vitamin D deficiency is associated with the risk of atopic diseases and respiratory infections. The activated vitamin D receptor (VDR) forms a dimer with the retinoid X receptor alpha (RXRA) and binds to VDR/RXRA composite elements (CEs) in enhancers of target genes. However, VDR/RXRA CEs are identified in only 11.5% of cases in ChIP-Seq peaks. Our hypothesis was that VDR could form a VDR-Partner complex with transcription factor for which CEs have not yet been identified. We utilized Web-MCOT to search for novel VDR/Partner CEs in regulatory DNA. The potential formation of the VDR-Partner protein complex was assessed using the AlphaFold machine learning model. Through real-time RT-PCR, we measured the expression of immune system genes in a culture of U937 macrophage-like cells incubated with the active metabolite of vitamin D, calcitriol. We have predicted novel VDR/NR2C2 and VDR/PPARG CEs in the regulatory regions of immune system genes. We found potential synergism of VDR/NR2C2 and VDR/RXRA CEs in relation to the IRF5 gene, as well as potential synergism of VDR/PPARG and VDR/RXRA CEs for MAPK13. Predicting new regulatory relationships through the identification of new potential VDR/Partner CEs may provide insight into the deep mechanisms of vitamin D involvement in the pathogenesis of atopic dermatitis, bronchial asthma, allergic rhinitis, and pulmonary infections.