Chromatin, DNA methylation and neuron gene regulation — the purpose of the package

Chromatin, DNA methylation and neuron gene regulation — the purpose of the package

PDF

J Psychiatry Neurosci 2005;30(4):257-63

Rajiv P. Sharma, MD; Dennis R. Grayson, PhD; Alessandro Guidotti, MD; Erminio Costa, MD

Ross — Women’s Mental Health and Addiction Research Section, Centre for Addiction and Mental Health; Murray — Division of Neurology, Sunnybrook and Women’s College Health Sciences Centre, Toronto; Steiner — Departments of Psychiatry and Behavioural Neurosciences and of Obstetrics and Gynecology, McMaster University, and Women’s Health Concerns Clinic, St. Joseph’s Healthcare, Hamilton, Ont.

Abstract

The accessibility of cognate binding sites within a gene promoter can be modified by the condensation or relaxation of local chromatin structure. Local chromatin structure is in turn programmed by covalent modifications of cytosine bases in DNA and amino acid residues in histone protein tails. These chemical and physical adaptations around gene promoters can significantly change levels of mRNA expression. Furthermore, linear patterns of covalent modification of histone protein tails are emerging as a distinct regulatory code — another form of cellular memory. Because chromatin structure can be modified by conventional pharmacologic therapy, a novel approach to the regulation of neuronal gene expression in clinical populations is possible.

Résumé

La condensation ou la relaxation de la structure locale de la chromatine peut modifier l’accessibilité des sites de liaison des cognats dans un promoteur génétique. Par ailleurs, les modifications covalentes des bases de cytosine dans l’ADN et des résidus d’acides aminés dans les queues d’histone programment la structure locale de la chromatine. Ces mécanismes d’adaptation chimique et physique qui entourent les promoteurs génétiques peuvent modifier considérablement les taux d’expression de l’ARNm. De plus, il apparaît que des motifs linéaires de modification covalente des queues d’histone forment un code distinct de régulation — une autre forme de mémoire cellulaire. Parce que la pharmacothérapie conventionnelle permet de modifier la structure de la chromatine, une démarche nouvelle de régulation de l’expression génétique neuronale dans les populations cliniques est possible.


Medical subject headings: neurons; chromatin; methylation; cognition; schizophrenia; bipolar disorder.

Submitted July 29, 2004; Revised Feb. 16, 2005; Accepted Feb. 22, 2005

Acknowledgements: This work was supported in part by NIMH- 069839 (R.P.S.), NIMH-62682 (D.R.G.), NIMH-062188 (A.G.) and NIMH-62090 (E.C.) from the National Institute of Mental Health.

Competing interests: None declared by Drs. Grayson, Guidotti and Costa. Dr. Sharma has received speaker fees from Abbott Laboratories.

Contributors: All of the authors made substantial contributions to the conception and design of the study, the acquisition or analysis of the data, and the drafting or revision of the article. Each author gave final approval for the article to be published.

Correspondence to: Dr. Rajiv P. Sharma, The Psychiatric Institute, University of Illinois at Chicago, 1601 W Taylor St., Chicago IL 60612; fax 312 413-4503; rsharma@psych.uic.edu