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Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
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VDR/RXR antagonizes calcineurin-activated NFAT1, an essential regulator of Coronin-1A expression and Mycobacterial

Sayantani Datta1, Arnab Hazra1, Payel Das1

  • 1Molecular Immunology and Cellular Microbiology Laboratory, Department of Bioscience and Biotechnology, Indian Institute of Technology Kharagpur, West Bengal, India.

The Biochemical Journal
|June 24, 2026
PubMed

Insights

Vitamin D3 and Retinoic Acid repress Coronin-1A (CORO1A) transcription by displacing NFAT1. Targeting this pathway enhances macrophage ability to clear mycobacteria, offering new therapeutic strategies.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Coronin-1A (CORO1A) is crucial for immune responses and host-pathogen interactions.
  • Mechanisms regulating CORO1A expression were previously unknown.

Purpose of the Study:

  • To elucidate the transcriptional regulation of CORO1A.
  • To identify factors controlling CORO1A expression in immune cells.

Main Methods:

  • Luciferase reporter assays to assess promoter activity.
  • Chromatin immunoprecipitation (ChIP) to identify protein-DNA interactions.
  • Electrophoretic Mobility Shift Assays (EMSA) to study transcription factor binding.

Main Results:

  • Vitamin D3 (VitD3) and Retinoic Acid (RA) repress CORO1A transcription.
  • NFAT1 is the primary driver of CORO1A in myeloid cells; NFAT1/NFAT2 in lymphoid cells.
  • VDR/RXR heterodimers competitively displace NFAT1 from the CORO1A promoter.
  • Inhibition of the calcineurin-NFAT1 pathway reduces CORO1A and enhances mycobacterial clearance.

Conclusions:

  • Discovered a novel competitive displacement mechanism for CORO1A transcriptional regulation.
  • Identified lineage-specific transcriptional circuitry for CORO1A.
  • The calcineurin-NFAT1 pathway is a potential therapeutic target for infectious diseases.
Keywords:
Coronin1ANFAT1VitaminD3calcineurinretinoic acid

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