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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Swahari, V; Nakamura, A; Hollville, E; Stroud, H; Simon, JM; Ptacek, TS; Beck, MV; Flowers, C; Guo, J; Plestant, C; Liang, J; Kurtz, CL; Kanke, M; Hammond, SM; He, Y-W; Anton, ES; Sethupathy, P; Moy, SS; Greenberg, ME; Deshmukh, M

Published Date

  • April 6, 2021

Published In

Volume / Issue

  • 35 / 1

Start / End Page

  • 108946 -

PubMed ID

  • 33826889

Pubmed Central ID

  • PMC8103628

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2021.108946


  • eng

Conference Location

  • United States