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Two nuclear signalling pathways for vitamin D

C Carlberg¹, I Bendik, A Wyss

¹Department of Pharma Research New Technologies, F. Hoffmann-La Roche Ltd, Basel, Switzerland.

|February 18, 1993

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Vitamin D3

Area of Science:

Molecular Biology
Endocrinology
Genetics

Background:

Vitamin D3's active form, 1,25-dihydroxy-D3, regulates gene expression via intracellular receptors.
These receptors are part of the steroid receptor superfamily and function as ligand-dependent transcription factors.

Purpose of the Study:

To identify and characterize distinct classes of vitamin D response elements (VDREs).
To investigate the roles of the vitamin D receptor (VDR) and retinoid-X receptor-alpha (RXR-alpha) in regulating gene transcription.

Main Methods:

Analysis of DNA sequences conferring vitamin D inducibility.
Identification of motifs recognized by VDR alone and by VDR-RXR-alpha heterodimers.

Main Results:

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Two classes of VDREs were identified: one activated by VDR alone, the other synergistically by VDR and RXR-alpha.

Specific DNA motifs and spacing patterns were associated with each class of response element.

Co-regulation by RXR depends on the presence of its ligand and the specific response element sequence.

Conclusions:

The nature of the response element and the presence of RXR ligands dictate nuclear receptor co-regulation.
This provides a deeper understanding of vitamin D and retinoid signaling pathways.