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Epigenetics

Methylation and schizophrenia

Nature Reviews Neuroscience volume 8, page 911 (2007)Cite this article

The authors showed that during maturation of the human prefrontal cortex (PFC), which starts prenatally and continues into puberty, there is a progressive increase in the number of GABAergic mRNA transcripts, including glutamic acid decarboxylase 1 (GAD1), a key enzyme for GABA synthesis. These increases were associated with chromatin remodelling, as an increase in histone H3 Lys4 (H3K4) methylation at GABAergic gene loci was also observed over this period of development.

Akbarian and colleagues found similar results in the mouse cerebral cortex, and so used mice to investigate the mechanism by which the H3K4 methylation of GABAergic chromatin occurs. Of the multiple histone methyltransferases that are expressed in mammals, only mixed lineage leukaemia 1 (MLL1) is strongly expressed in the adult human PFC and the mouse cerebral cortex. Examination of samples of cerebral cortex taken from adult Mll1+/− mice revealed a decrease in H3K4 methylation at the promoters of GABAergic genes. However, as the levels of the corresponding GABAergic mRNAs did not change, MLL1 might function downstream from the transcriptional process to regulate GABAergic gene expression.

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ORIGINAL RESEARCH PAPER

  1. Huang, H.-S. et al. Prefrontal dysfunction in schizophrenia involves mixed-lineage leukemia 1-regulated histone methylation at GABAergic gene promoters. J. Neurosci. 27, 11254–11262 (2007)

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Authors
  1. Monica Hoyos Flight
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Flight, M. Methylation and schizophrenia. Nat Rev Neurosci 8, 911 (2007). https://doi.org/10.1038/nrn2282

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