In mammals, the environment plays a critical role in promoting the final steps in neuronal development 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.

中文翻译：

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神经元中的早期生命基因表达调节持久的表观遗传状态。

在哺乳动物中，环境在促进出生后早期神经元发育的最终步骤中起着至关重要的作用。虽然表观遗传因素有助于这一过程，但对潜在的分子机制仍知之甚少。在这里，我们显示了在早期的大脑中，DNA甲基转移酶DNMT3A会短暂地跨低表达基因的转录区域结合，其结合确定了这些基因中CA序列（mCA）处的DNA甲基化模式。我们发现，DNMT3A的占用和基因转录区域内的mCA沉积受到基因转录的负调控，并且可能会受到早期生活经验的影响。一旦存入，