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

Alexey V Popov1, Dmitry Yu Oshchepkov2, Vladislav V Kononchuk1

  • 1Institute of Molecular Biology and Biophysics, Federal Research Center of Fundamental and Translational Medicine, Novosibirsk 630060, Russia.

Insights

Vitamin D receptor (VDR) may partner with other factors, not just RXRA, to regulate immune genes. This discovery offers new insights into vitamin D

Area of Science:

  • Molecular Biology
  • Immunology
  • Genetics

Background:

  • Vitamin D deficiency is linked to atopic diseases and respiratory infections.
  • Activated vitamin D receptor (VDR) typically dimerizes with RXRA to bind DNA enhancers, but known binding sites are limited.
  • The hypothesis posits VDR may form complexes with other transcription factors to regulate gene expression.

Purpose of the Study:

  • To identify novel VDR/Partner composite elements (CEs) in regulatory DNA.
  • To explore potential VDR protein-protein interactions with novel partners.
  • To investigate the role of these interactions in immune gene regulation.

Main Methods:

  • Web-MCOT tool used to search for novel VDR/Partner CEs.
  • AlphaFold model assessed potential VDR-Partner protein complex formation.
  • Real-time RT-PCR measured immune gene expression in U937 cells treated with calcitriol.

Main Results:

  • Novel VDR/NR2C2 and VDR/PPARG CEs predicted in immune gene regulatory regions.
  • Potential synergistic interactions identified between VDR/NR2C2 and VDR/RXRA for IRF5.
  • Potential synergistic interactions identified between VDR/PPARG and VDR/RXRA for MAPK13.

Conclusions:

  • VDR likely forms complexes with novel partners like NR2C2 and PPARG.
  • These novel VDR/Partner CEs may explain vitamin D's role in immune gene regulation.
  • Findings may elucidate vitamin D's role in atopic dermatitis, asthma, rhinitis, and infections.

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