MicroRNA-29 is an essential regulator of brain maturation through regulation of CH methylation.

Autor:	Swahari V; Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA. Electronic address: swahari@email.unc.edu., Nakamura A; Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA; Neurobiology Curriculum, University of North Carolina, Chapel Hill, NC, USA., Hollville E; Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA., Stroud H; Department of Neurobiology, Harvard University, Boston, MA, USA., Simon JM; Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA; Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC, USA., Ptacek TS; Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA; Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC, USA., Beck MV; Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA., Flowers C; Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA., Guo J; Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA., Plestant C; Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA., Liang J; Department of Immunology, Duke University, Durham, NC, USA., Kurtz CL; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA., Kanke M; Department of Biomedical Sciences, Cornell University, Ithaca, NY, USA., Hammond SM; Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC, USA., He YW; Department of Immunology, Duke University, Durham, NC, USA., Anton ES; Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA; Neurobiology Curriculum, University of North Carolina, Chapel Hill, NC, USA; Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC, USA., Sethupathy P; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA; Department of Biomedical Sciences, Cornell University, Ithaca, NY, USA., Moy SS; Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA; Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC, USA., Greenberg ME; Department of Neurobiology, Harvard University, Boston, MA, USA., Deshmukh M; Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA; Neurobiology Curriculum, University of North Carolina, Chapel Hill, NC, USA; Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC, USA; Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC, USA. Electronic address: mohanish@med.unc.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2021 Apr 06; Vol. 35 (1), pp. 108946.
DOI:	10.1016/j.celrep.2021.108946
Abstrakt:	Although embryonic brain development and neurodegeneration have received considerable attention, the events that govern postnatal brain maturation are less understood. Here, we identify the miR-29 family to be strikingly induced during the late stages of brain maturation. Brain maturation is associated with a transient, postnatal period of de novo non-CG (CH) DNA methylation mediated by DNMT3A. We examine whether an important function of miR-29 during brain maturation is to restrict the period of CH methylation via its targeting of Dnmt3a. Deletion of miR-29 in the brain, or knockin mutations preventing miR-29 to specifically target Dnmt3a, result in increased DNMT3A expression, higher CH methylation, and repression of genes associated with neuronal activity and neuropsychiatric disorders. These mouse models also develop neurological deficits and premature lethality. Our results identify an essential role for miR-29 in restricting CH methylation in the brain and illustrate the importance of CH methylation regulation for normal brain maturation. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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