Submillimolar levels of calcium regulates DNA structure at the dinucleotide repeat (TG/AC)n
- Molecular Control of Neurodifferentiation, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892
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Communicated by Bernhard Witkop, National Institute of Diabetes, Bethesda, MD (received for review November 6, 1997)
Abstract
Submillimolar levels of calcium, similar to the physiological total (bound + free) intranuclear concentration (0.01–1 mM), induced a conformational change within d(TG/AC)n, one of the frequent dinucleotide repeats of the mammalian genome. This change is calcium-specific, because no other tested cation induced it and it was detected as a concentration-dependent transition from B- to a non-B-DNA conformation expanding from 3′ end toward the 5′ of the repeat. Genomic footprinting of various rat brain regions revealed the existence of similar non-B-DNA conformation within a d(TG/AC)28 repeat of the endogenous enkephalin gene only in enkephalin-expressing caudate nucleus and not in the nonexpressing thalamus. Binding assays demonstrated that DNA could bind calcium and can compete with calmodulin for calcium.
Footnotes
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↵ * To whom reprint requests should be addressed at: Department of Anatomy and Cell Biology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814. e-mail: vagoston{at}helix.nih.gov.
- ABBREVIATIONS:
- ENK,
- enkephalin;
- BAPTA = 1,
- 2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid;
- CaM,
- calmodulin;
- CaM-PK II,
- CaM protein kinase II
