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

Vijay Swahari; Ayumi Nakamura; Emilie Hollville; Hume Stroud; Jeremy M. Simon; Travis S. Ptacek; Matthew V. Beck; Cornelius Flowers; Jiami Guo; Charlotte Plestant; Jie Liang; C. Lisa Kurtz; Matt Kanke; Scott M. Hammond; You-Wen He; E.S. Anton; Praveen Sethupathy; Sheryl S. Moy; Michael E. Greenberg; Mohanish Deshmukh

Cell Reports (Apr 2021)

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

Vijay Swahari,
Ayumi Nakamura,
Emilie Hollville,
Hume Stroud,
Jeremy M. Simon,
Travis S. Ptacek,
Matthew V. Beck,
Cornelius Flowers,
Jiami Guo,
Charlotte Plestant,
Jie Liang,
C. Lisa Kurtz,
Matt Kanke,
Scott M. Hammond,
You-Wen He,
E.S. Anton,
Praveen Sethupathy,
Sheryl S. Moy,
Michael E. Greenberg,
Mohanish Deshmukh

Affiliations

Vijay Swahari: Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA; Corresponding author
Ayumi Nakamura: Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA; Neurobiology Curriculum, University of North Carolina, Chapel Hill, NC, USA
Emilie Hollville: Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA
Hume Stroud: Department of Neurobiology, Harvard University, Boston, MA, USA
Jeremy M. Simon: 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
Travis S. Ptacek: Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA; Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC, USA
Matthew V. Beck: Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA
Cornelius Flowers: Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA
Jiami Guo: Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA
Charlotte Plestant: Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA
Jie Liang: Department of Immunology, Duke University, Durham, NC, USA
C. Lisa Kurtz: Department of Genetics, University of North Carolina, Chapel Hill, NC, USA
Matt Kanke: Department of Biomedical Sciences, Cornell University, Ithaca, NY, USA
Scott M. Hammond: Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC, USA
You-Wen He: Department of Immunology, Duke University, Durham, NC, USA
E.S. Anton: 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
Praveen Sethupathy: Department of Genetics, University of North Carolina, Chapel Hill, NC, USA; Department of Biomedical Sciences, Cornell University, Ithaca, NY, USA
Sheryl S. Moy: Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA; Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC, USA
Michael E. Greenberg: Department of Neurobiology, Harvard University, Boston, MA, USA
Mohanish Deshmukh: 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; Corresponding author

Journal volume & issue: Vol. 35, no. 1
p. 108946

Abstract

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Summary: 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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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