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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


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.

Original languageEnglish
Article number108946
JournalCell Reports
Issue number1
Early online date6 Apr 2021
Publication statusPublished - 6 Apr 2021


  • autism
  • CH methylation
  • DNMT3A
  • epilepsy
  • MeCP2
  • miR-29
  • miRNA
  • neurodevelopmental disorders
  • non-CG methylation
  • seizures


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