Examining the links between neuronal activity, transcriptional output, and synaptic function offers unique insights into how neurons adapt to changing environments and form memories. Epigenetic markers, such as DNA methylation and histone modifications, have been implicated in the formation of not only cellular memories such as cell fate, but also memories of experience at the organismal level. Here, we review recent advances in chromatin regulation that contribute to synaptic plasticity and drive adaptive behaviors through dynamic and precise regulation of transcription output in neurons. We discuss chromatin-associated proteins, histone variant proteins, the contribution of cis-regulatory elements and their interaction with histone modifications, and how these mechanisms are integrated into distinct behavior and environmental response paradigms.
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