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

First Author  Swahari V Year  2021
Journal  Cell Rep Volume  35
Issue  1 Pages  108946
PubMed ID  33826889 Mgi Jnum  J:306547
Mgi Id  MGI:6716745 Doi  10.1016/j.celrep.2021.108946
Citation  Swahari V, et al. (2021) MicroRNA-29 is an essential regulator of brain maturation through regulation of CH methylation. Cell Rep 35(1):108946
abstractText  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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