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Cell. 2017 Nov 16;171(5):1151-1164.e16. doi: 10.1016/j.cell.2017.09.047. Epub 2017 Oct 19.

Early-Life Gene Expression in Neurons Modulates Lasting Epigenetic States.

Author information

1
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
2
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: michael_greenberg@hms.harvard.edu.

Abstract

In mammals, the environment plays a critical role inĀ promoting the final steps in neuronal developmentĀ during the early postnatal period. While epigenetic factors are thought to contribute to this process, the underlying molecular mechanisms remain poorly understood. Here, we show that in the brain during early life, the DNA methyltransferase DNMT3A transiently binds across transcribed regions of lowly expressed genes, and its binding specifies the pattern of DNA methylation at CA sequences (mCA) within these genes. We find that DNMT3A occupancy and mCA deposition within the transcribed regions of genes is negatively regulated by gene transcription and may be modified by early-life experience. Once deposited, mCA is bound by the methyl-DNA-binding protein MECP2 and functions in a rheostat-like manner to fine-tune the cell-type-specific transcription of genes that are critical for brain function.

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PMID:
29056337
PMCID:
PMC5693680
[Available on 2018-11-16]
DOI:
10.1016/j.cell.2017.09.047
[Indexed for MEDLINE]

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