Title

Epigenetic regulation in human brain-focus on histone lysine methylation

PubMed ID

18814864

UMMS Affiliation

Department of Psychiatry

Date

2-26-2009

Document Type

Article

Subjects

Brain Chemistry; Gene Expression Regulation; Histones; Humans; Lysine; Mental Disorders; Methylation; RNA

Disciplines

Life Sciences | Medicine and Health Sciences | Neuroscience and Neurobiology

Abstract

Alterations in RNA levels are frequently reported in brain of subjects diagnosed with autism, schizophrenia, depression, and other psychiatric diseases, but it remains unclear whether the underlying molecular pathology involves changes in gene expression, as opposed to alterations in messenger RNA processing. Pre-clinical studies have revealed that stress, drugs, and a variety of other environmental factors lead to changes in RNA levels in brain via epigenetic mechanisms, including modification of histone proteins. A number of site-specific modifications of the nucleosome core histones-including the trimethylated forms of histone H3 lysines K4, K9, and K27-are of particular interest for postmortem research, because these marks differentiate between active and inactive chromatin and seem to remain relatively stable during tissue autolysis. Therefore, histone methylation profiling at promoter regions could provide important clues about mechanisms of gene expression in human brain during development and in disease. Intriguingly, mutations within the genes encoding the H3K9-specific methyltransferase, EHMT1, and the H3K4-specific histone demethylase, JARID1C/SMCX, have been linked to mental retardation and autism, respectively. In addition, the H3K4-specific methyltransferase, MLL1, is essential for hippocampal synaptic plasticity and might be involved in cortical dysfunction of some cases of schizophrenia. Together, these findings emphasize the potential significance of histone lysine methylation for orderly brain development and also as a molecular toolbox to study chromatin function in postmortem tissue.

Rights and Permissions

Citation: Biol Psychiatry. 2009 Feb 1;65(3):198-203. Epub 2008 Sep 24. Link to article on publisher's site

Comments

Co-author Hsien-Sung Huang is a student in the Neuroscience program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.

Related Resources

Link to Article in PubMed