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University of North Carolina-Chapel Hill: Dataset Details, ID=GSE140163

Superfund Research Program

Molecular Drivers of Arsenic-Induced Diabetes

Project Leader: Praveen Sethupathy (Cornell University)
Co-Investigators: Miroslav Styblo, Rebecca C. Fry, Fei Zou
Grant Number: P42ES031007
Funding Period: 2020-2025
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Title: MicroRNA-29 is an essential regulator of non-CG methylation during brain maturation [RNA-seq]

Accession Number: GSE140163

Link to Dataset:

Repository: Gene Expression Omnibus (GEO)

Data Type(s): Gene Expression

Experiment Type(s): Expression profiling by high throughput sequencing

Organism(s): Mus musculus

Summary: While embryonic brain development and neurodegeneration have been examined extensively, the events that govern postnatal brain maturation are less understood. During this period, widespread changes in synaptic connectivity are evident1,2 and, perturbations of synaptic development or maturation can have severe neurobehavioral consequences as seen in autism spectrum disorders (ASD), epilepsy and schizophrenia3-6. Recent studies have led to the unexpected discovery that marked increases in non-canonical (non-CG) DNA methylation occur during postnatal brain maturation7-14. This de novo CH methylation (where H= A, C, T), which occurs 1-4 weeks postnatally in mice and 1-15 years in humans7, is important for experience-dependent fine tuning of gene expression15 . The critical period of CH methylation appears to be mediated by Dnmt3a, the DNA methyltransferase that catalyzes CH methylation8,9. During brain maturation, Dnmt3a levels are elevated and then sharply decline7,16, and a strict control of CH methylation seems important as mutations or variants of Dnmt3a are associated with ASD, epilepsy and intellectual disability17-19. Here we identify the microRNA miR-29 as an essential regulator of Dnmt3a and CH methylation during brain maturation. Mice deficient in miR-29 or mice in which miR-29 can no longer target Dnmt3a exhibit enhanced levels of Dnmt3a, global CH hypermethylation, and repression of neuronal genes specifically associated with synaptic activity and neurotransmission. Importantly, these mice appear normal at birth, but subsequently exhibit severe neurological deficits including susceptibility to seizures and premature lethality. Together, these results identify an essential function of miR-29 in defining the critical period of DNA methylation during brain maturation, the absence of which results in neurobehavioral deficits.

Publication(s) associated with this dataset:
  • 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, Anton E, Sethupathy P, Moy SS, Greenberg ME, Deshmukh M. 2021. MicroRNA-29 is an essential regulator of brain maturation through regulation of CH methylation. Cell Rep 35(1):doi:10.1016/j.celrep.2021.108946 PMID:33826889 PMCID:PMC8103628
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