Journal article
Epigenetic regulation of the calcitonin gene-related peptide gene in trigeminal glia
Cephalalgia, Vol.31(5), pp.614-624
04/2011
DOI: 10.1177/0333102410391487
PMCID: PMC3383834
PMID: 21216873
Abstract
The neuropeptide calcitonin gene-related peptide (CGRP) plays a key role in migraine. CGRP gene expression involves an enhancer that is active in neurons, yet inactive in glia. In this report, we analyze epigenetic modifications that allow enhancer activation in glia.
DNA methylation and histone acetylation states were measured in rat and human- model cell lines and primary cultures of rat trigeminal ganglia glia. The functional consequence of altering the chromatin state was determined by quantitative measurements of both calcitonin (CT) and CGRP mRNAs.
A hypermethylated CpG island flanking the enhancer was identified in glia and non-expressing cell lines. In addition, the chromatin was hypoacetylated. Treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine induced CT mRNA ~30-fold in glial cultures. Treatment with a histone deacetylase inhibitor alone had little effect; however, the combination of inhibitors yielded a synergistic ~80-fold increase in CT and ~threefold increase in CGRP mRNA. Treated glia contained CT precursor (pro-CT) immunoreactivity.
Epigenetic modulation is sufficient to induce the CGRP gene in glia. Because the CGRP gene is systemically activated by inflammatory conditions, this suggests that glial pro-CT may be an unexplored biomarker during migraine.
Details
- Title: Subtitle
- Epigenetic regulation of the calcitonin gene-related peptide gene in trigeminal glia
- Creators
- Ki-Youb Park - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USAJoshua R FletcherAnn C RaddantAndrew F Russo
- Resource Type
- Journal article
- Publication Details
- Cephalalgia, Vol.31(5), pp.614-624
- DOI
- 10.1177/0333102410391487
- PMID
- 21216873
- PMCID
- PMC3383834
- NLM abbreviation
- Cephalalgia
- ISSN
- 0333-1024
- eISSN
- 1468-2982
- Publisher
- England
- Grant note
- T32GM073610 / NIGMS NIH HHS R01 NS075599 / NINDS NIH HHS R01 DE016511 / NIDCR NIH HHS T32 GM073610 / NIGMS NIH HHS R01DE016511 / NIDCR NIH HHS
- Language
- English
- Date published
- 04/2011
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center
- Record Identifier
- 9984020898502771
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