MicroRNA-29 is an Essential Regulator of Brain Maturation Through Regulation of CH Methylation

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2021 Apr 7

PMID 33826889

Citations 24

Authors

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

Soon will be listed here.

Abstract

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.

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