RE1containing

RE1-containing refers to DNA elements, often called RE1 or NRSE (repressor element 1/neuron-restrictive silencing element), located in or near a gene’s regulatory regions and capable of binding the transcriptional repressor REST (also called NRSF). When REST binds to an RE1/NRSE site, transcription of the associated gene is repressed in cells where REST is active, especially non-neuronal cells and immature neural progenitors. In neuronal cells, REST expression declines, allowing RE1-containing neuronal genes to be expressed.

Location and structure: RE1 elements are short, degenerate sequences typically about 9 base pairs long, with a consensus motif that varies slightly among species. They can reside in promoters, enhancers, introns, or intergenic regions, and a single gene can contain multiple RE1 sites, contributing to complex regulation of transcription across tissues and developmental stages.

Mechanism: REST recruits corepressor complexes including CoREST and Sin3, and chromatin-modifying enzymes such as LSD1 and histone deacetylases. These interactions promote histone deacetylation and chromatin condensation, reducing transcriptional initiation at the bound gene. Regulation of REST activity and RE1 occupancy is dynamic during development and in response to signaling cues.

Biological significance: The RE1/REST axis is a key mechanism to keep neuronal genes off in non-neuronal cells and to fine-tune their timing during neural development. The density and composition of RE1 sites across the genome contribute to the neuronal gene expression program and neuronal identity.

Clinical relevance: Altered REST/RE1 signaling has been linked to cancer, neurodevelopmental disorders, and neurodegenerative diseases. Abnormal REST levels can shift neuronal gene expression patterns and affect cell fate, making RE1-containing genes a focus of biomedical research.