Transcriptional Regulation of Neuronal Gene Expression

Transcriptional regulation in neurons orchestrates the precise activation and repression of gene networks that underlie neuronal identity, synaptic function and plasticity. Central to this process are transcription factors that recognise specific DNA motifs and recruit chromatin-modifying enzymes to alter histone marks, DNA methylation and nucleosome positioning. Epigenetic modifications such as histone acetylation and methylation modulate chromatin accessibility, enabling rapid responses to developmental cues and neuronal activity. The RE1-silencing transcription factor (REST) exemplifies a master regulator that silences neuronal genes in non-neuronal contexts by recruiting corepressor complexes and histone deacetylases. Conversely, activity-dependent transcription factors such as CREB and immediate early genes promote gene expression in response to synaptic signalling. Alternative splicing and non-coding RNAs further diversify the transcriptome, allowing single genes to generate multiple functional isoforms that fine-tune neuronal functions. Dysregulation of any component—from transcription factors and chromatin modifiers to splicing regulators—can disrupt neuronal differentiation, contribute to neurodevelopmental disorders and drive neurodegeneration. Recent advances in genome-wide profiling, single-cell transcriptomics and epigenome editing have illuminated the dynamic interplay between DNA sequence, chromatin state and external stimuli in directing neuronal gene programmes.

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Transcriptional Regulation of Neuronal Gene Expression publication trend

The graph below shows the total number of articles in transcriptional regulation of neuronal gene expression across all publications each year (not limited to Nature Index journals).

Technical terms

Transcription factor: A protein that binds specific DNA sequences to regulate the transcription of genetic information.

Epigenetic modification: A heritable change in gene function without alteration of the DNA sequence, often via histone or DNA chemical marks.

Chromatin remodelling: The dynamic repositioning or restructuring of nucleosomes to regulate DNA accessibility for transcription.

DNA methylation: Addition of methyl groups to cytosine bases, typically leading to repression of gene expression.

Alternative splicing: The process by which different combinations of exons are joined to produce multiple mRNA variants from a single gene.

RE1-silencing transcription factor (REST): A master repressor that binds RE1 sites to silence neuronal genes in non-neuronal cells and modulate gene networks in neurons.

References

1. SIRT6-dependent functional switch via K494 modifications of RE-1 silencing transcription factor. Cell Death & Disease (2024).
2. Comprehensive analysis of the REST transcription factor regulatory networks in IDH mutant and IDH wild-type glioma cell lines and tumors. Acta Neuropathologica Communications (2024).
3. Targeting of REST with rationally-designed small molecule compounds exhibits synergetic therapeutic potential in human glioblastoma cells. BMC Biology (2024).