TY - JOUR

T1 - Search for Potential VDR/Partner Composite Elements in Regulatory DNA of Genes Associated with Respiratory Infections and Atopic Diseases

AU - Popov, Alexey V.

AU - Oshchepkov, Dmitry Yu

AU - Kononchuk, Vladislav V.

AU - Kalinina, Tatiana S.

AU - Valembakhov, Ilya S.

AU - Lukin, Alexander D.

AU - Kondyurina, Elena G.

AU - Zelenskaya, Vera V.

AU - Vavilin, Valentin

N1 - The study was supported by Russian-government funding for basic research at the Federal Research Center of Fundamental and Translational Medicine (No. 125031203556-7). The work was performed using the equipment of the Center for Collective Use “Proteomic Analysis”.

PY - 2026

Y1 - 2026

N2 - 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.

AB - 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.

KW - NR2C2

KW - PPARG

KW - VDR

KW - atopy

KW - composite elements

KW - lung infection

UR - https://www.scopus.com/pages/publications/105027011075

UR - https://www.mendeley.com/catalogue/d6bad78f-b3ec-360e-8083-22cedbca3030/

U2 - 10.3390/ijms27010409

DO - 10.3390/ijms27010409

M3 - Article

C2 - 41516283

VL - 27

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 1

M1 - 409

ER -