DNA Methylation-Mediated Modulation of Endocytosis as Potential Mechanism for Synaptic Function Regulation in Murine Inhibitory Cortical Interneurons.

Cerebral Cortex
Daniel PensoldGeraldine Zimmer-Bensch

Abstract

The balance of excitation and inhibition is essential for cortical information processing, relying on the tight orchestration of the underlying subcellular processes. Dynamic transcriptional control by DNA methylation, catalyzed by DNA methyltransferases (DNMTs), and DNA demethylation, achieved by ten-eleven translocation (TET)-dependent mechanisms, is proposed to regulate synaptic function in the adult brain with implications for learning and memory. However, focus so far is laid on excitatory neurons. Given the crucial role of inhibitory cortical interneurons in cortical information processing and in disease, deciphering the cellular and molecular mechanisms of GABAergic transmission is fundamental. The emerging relevance of DNMT and TET-mediated functions for synaptic regulation irrevocably raises the question for the targeted subcellular processes and mechanisms. In this study, we analyzed the role dynamic DNA methylation has in regulating cortical interneuron function. We found that DNMT1 and TET1/TET3 contrarily modulate clathrin-mediated endocytosis. Moreover, we provide evidence that DNMT1 influences synaptic vesicle replenishment and GABAergic transmission, presumably through the DNA methylation-dependent transcription...Continue Reading

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Citations

May 23, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Judit SymmankGeraldine Zimmer-Bensch
Aug 6, 2020·International Journal of Molecular Sciences·Cathrin BayerGeraldine Zimmer-Bensch
Aug 15, 2020·Frontiers in Cell and Developmental Biology·Anne HahnGeraldine Zimmer-Bensch
Oct 13, 2020·Frontiers in Neuroscience·Jenice Linde, Geraldine Zimmer-Bensch
Mar 7, 2021·International Journal of Molecular Sciences·Sarah BachmannGeraldine Zimmer-Bensch
Apr 29, 2021·Neural Regeneration Research·Daniel Pensold, Geraldine Zimmer-Bensch
May 14, 2021·Molecular Genetics & Genomic Medicine·Xiaoman ZhangHaiyan Wei

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Methods Mentioned

BETA
fluorescent
activated cell sorting
Immunoprecipitation
transgenic
genotyping
transfections
transfection
Reverse Transcription PCR
PCR
density gradient centrifugation

Software Mentioned

BaseCaller
samtools
Signal
Illumina CASAVA
htseq
Windows
R package pathview
UCSC genome browser
Illumina BeadStudio
Fiji

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