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Hyperosmolarity-induced gene stimulation is mediated by the negative calcium responsive element
T Okazaki1, T Ishikawa, S Nishimori
1Endocrine Genetics and Hypertension Unit, 4th Department of Internal Medicine, University of Tokyo School of Medicine, Bunkyo-ku, Tokyo 112, Japan. okbgeni-tky@umin.u-tokyo.ac
The Journal of Biological Chemistry
|January 24, 1998
Summary
Hyperosmolarity, induced by sodium chloride, reduces nuclear protein binding to oligo B DNA elements. This leads to increased transcription of vasoactive genes, revealing a novel regulatory mechanism in gene expression.
Area of Science:
- Molecular Biology
- Gene Regulation
- Cellular Physiology
Background:
- Negative calcium-responsive elements (Ca2+e) in genes like parathyroid hormone bind nuclear proteins dependent on extracellular calcium.
- Oligo B, a specific DNA element, is found in the 5'-flanking regions of vasoactive genes, including vasopressin and atrial natriuretic polypeptide.
- Oligo B-like sequences are evolutionarily conserved, suggesting functional importance.
Purpose of the Study:
- To investigate the role of oligo B in gene regulation by hyperosmolarity.
- To determine if cell volume changes, induced by hyperosmolarity, affect oligo B DNA-protein interactions.
- To elucidate the molecular mechanisms underlying hyperosmolarity-mediated gene expression changes.
Main Methods:
- Utilized cultured cells to study gene regulation under hyperosmolar conditions.
- Assessed the binding affinity of nuclear proteins to oligo B using sodium chloride and urea to induce hyperosmolarity.
- Employed potato acid phosphatase to investigate the role of protein phosphorylation in regulating oligo B binding.
Main Results:
- Hyperosmolarity induced by sodium chloride, but not urea, significantly reduced the binding of nuclear proteins, including redox factor 1, to oligo B.
- Dephosphorylation of nuclear proteins reversed the attenuated binding, indicating NaCl-induced phosphorylation weakens oligo B binding.
- These molecular events correlated with hyperosmolarity-mediated transcriptional stimulation of genes containing the oligo B element.
Conclusions:
- Oligo B acts as a crucial mediator in hyperosmolarity-induced gene regulation.
- Sodium chloride-induced hyperosmolarity triggers phosphorylation of nuclear proteins, diminishing their binding to oligo B and subsequently upregulating gene transcription.
- This study uncovers a novel pathway linking cell volume changes to gene expression modulation via specific DNA-protein interactions.
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