Reviewing the role of DNA (cytosine-5) methyltransferase overexpression in the cortical GABAergic dysfunction associated with psychosis vulnerability

Erminio Costa, Erbo Dong, Dennis R. Grayson, Alessandro Guidotti, William Ruzicka, Marin D Veldic

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

In this review, we discuss changes in the regulation of gene expression in the central nervous system (CNS) associated with DNA (cytosine-5) methylation, chromatin remodeling and post-translational covalent modifications of histones. During brain development, abnormal intrinsic or extrinsic cues may compromise epigenetic processes regulating neural stem cell proliferation and differentiation and thus directly or indirectly could contribute to altered epiphenotypes leading to psychiatric disorders. These mechanisms, that include chromatin remodeling and reversible changes in promoter methylation patterns, are largely expressed by terminally differentiated cortical GABAergic neurons. These neurons are unique among various brain cell subtypes because they express high levels of DNA-methyltransferase-1 (DNMT1). Moreover, DNMT1 expression is further increased in schizophrenia (SZ) and bipolar (BP) disorder brains. To unravel how this pathological DNMT1 overexpression induces GABAergic neuronal dysfunction in SZ and in other psychoses, we report on how alterations in methylation modify the expression of susceptible vulnerability genes such as reelin or GAD67 in these neurons. The results encourage the view that promoter hypermethylation in GABAergic neurons that occurs in SZ represents a testable target for novel therapeutic strategies to treat this disorder.

Original languageEnglish (US)
Pages (from-to)29-36
Number of pages8
JournalEpigenetics
Volume2
Issue number1
StatePublished - Jan 2007
Externally publishedYes

Fingerprint

DNA (Cytosine-5-)-Methyltransferase
Psychotic Disorders
Methyltransferases
Methylation
GABAergic Neurons
Schizophrenia
Chromatin Assembly and Disassembly
DNA
Brain
Genetic Epigenesis
Neurons
Neural Stem Cells
Cytosine
Gene Expression Regulation
Post Translational Protein Processing
Bipolar Disorder
Histones
Cues
Psychiatry
Cell Differentiation

Keywords

  • DNA-methyltransferase 1
  • GABAergic neurons
  • GAD67
  • Psychosis
  • Reelin
  • Schizophrenia

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Reviewing the role of DNA (cytosine-5) methyltransferase overexpression in the cortical GABAergic dysfunction associated with psychosis vulnerability. / Costa, Erminio; Dong, Erbo; Grayson, Dennis R.; Guidotti, Alessandro; Ruzicka, William; Veldic, Marin D.

In: Epigenetics, Vol. 2, No. 1, 01.2007, p. 29-36.

Research output: Contribution to journalArticle

Costa, Erminio ; Dong, Erbo ; Grayson, Dennis R. ; Guidotti, Alessandro ; Ruzicka, William ; Veldic, Marin D. / Reviewing the role of DNA (cytosine-5) methyltransferase overexpression in the cortical GABAergic dysfunction associated with psychosis vulnerability. In: Epigenetics. 2007 ; Vol. 2, No. 1. pp. 29-36.
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