A unique role for DNA (hydroxy)methylation in epigenetic regulation of human inhibitory neurons

Kozlenkov A, Li J, Apontes P, Hurd YL, Byne WM, Koonin E, Wegner M, Mukamel EA, Dracheva S (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Science Advances American Association for the Advancement of Science

Book Volume: 4

Journal Issue: 9

DOI: 10.1126/sciadv.aau6190

Abstract

Brain function depends on interaction of diverse cell types whose gene expression and identity are defined, in part, by epigenetic mechanisms. Neuronal DNA contains two major epigenetic modifications, methylcytosine (mC) and hydroxymethylcytosine (hmC), yet their cell type-specific landscapes and relationship with gene expression are poorly understood. We report high-resolution (h)mC analyses, together with transcriptome and histone modification profiling, in three major cell types in human prefrontal cortex: glutamatergic excitatory neurons, medial ganglionic eminence-derived γ-aminobutyric acid (GABA)ergic inhibitory neurons, and oligodendrocytes. We detected a unique association between hmC and gene expression in inhibitory neurons that differed significantly from the pattern in excitatory neurons and oligodendrocytes. We also found that risk loci associated with neuropsychiatric diseases were enriched near regions of reduced hmC in excitatory neurons and reduced mC in inhibitory neurons. Our findings indicate differential roles for mC and hmC in regulation of gene expression in different brain cell types, with implications for the etiology of human brain diseases.

Authors with CRIS profile

Michael Wegner Lehrstuhl für Biochemie und Pathobiochemie

Involved external institutions

James J. Peters VA Medical Center US United States (USA) (US) University of California, San Diego US United States (USA) (US) Icahn School of Medicine at Mount Sinai US United States (USA) (US) United States National Library of Medicine (NLM) US United States (USA) (US)

How to cite

APA:

Kozlenkov, A., Li, J., Apontes, P., Hurd, Y.L., Byne, W.M., Koonin, E.,... Dracheva, S. (2018). A unique role for DNA (hydroxy)methylation in epigenetic regulation of human inhibitory neurons. Science Advances, 4(9). https://dx.doi.org/10.1126/sciadv.aau6190

MLA:

Kozlenkov, Alexey, et al. "A unique role for DNA (hydroxy)methylation in epigenetic regulation of human inhibitory neurons." Science Advances 4.9 (2018).

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