What is the function of enhancers in gene expression?

From the Guidelines

Enhancers play a crucial role in gene expression by regulating the transcription of genes, particularly those involved in cellular development and response to environmental factors. The function of enhancers in gene expression is complex and multifaceted, involving the regulation of transcriptional activity in various cellular contexts 1.

Key Points

• Enhancers are short segments of DNA that can be located far away from the genes they regulate, and they can loop back to interact with promoters to enhance transcriptional activity.
• The study of DNA methylation clocks has shown that enhancers are often located in regions of the genome that are sensitive to environmental factors, such as diet and stress, and that changes in methylation patterns at these sites can be associated with aging and age-related diseases 1.
• The location of enhancers is assessed for overlap with functional categories, including promoter flanking, transcription start site, CTCF, weak enhancer, enhancer, transcribed region, and repressed regions, using tools such as the Core Encode Combined Chromatin Segmentation tracks 1.
• The overlap of CpGs from DNA methylation clocks with enhancer regions has been found to be significant, suggesting that enhancers play a key role in the regulation of gene expression during aging 1.

Implications

• The study of enhancers and their role in gene expression has important implications for our understanding of cellular development, aging, and age-related diseases.
• Further research is needed to fully elucidate the mechanisms by which enhancers regulate gene expression and to explore the potential therapeutic applications of this knowledge.
• The use of techniques such as whole-genome bisulfite sequencing and chromatin immunoprecipitation sequencing can provide valuable insights into the function of enhancers and their role in regulating gene expression 1.

From the Research

Function of Enhancers in Gene Expression

• Enhancers are short regulatory sequences bound by sequence-specific transcription factors and play a major role in the spatiotemporal specificity of gene expression patterns in development and disease 2.
• They are short DNA sequences that activate their target promoter from a distance, but increasing the genomic distance between the enhancer and the promoter decreases expression levels 3.
• Enhancers can be classified into different types, including classical enhancers and facilitators, which have distinct roles in activating target gene expression 4.
• The original definition of an enhancer is a DNA sequence that activates transcription independent of orientation and direction, but dissection of numerous enhancer loci has shown that many enhancer-like elements might not conform to this definition 5.

Mechanisms of Enhancer Function

• Enhancers can cooperate to compensate for loss of activity over large genomic distances, and synergy between two enhancer elements depends on the distance at which the two elements are integrated 3.
• Super-enhancers, which are compound regulatory elements that control expression of key cell identity genes, contain multiple constituent regulatory elements, including classical enhancers and facilitators 4.
• Active enhancers are bidirectionally transcribed to produce enhancer RNAs (eRNAs), which execute crucial tasks in regulating chromatin conformation and transcription activation 6.

Identification and Regulation of Enhancers

• Enhancers can be identified using epigenomic approaches, such as chromatin structure-based approaches and correlation-based approaches 2.
• The function of specific enhancers can be tested experimentally by perturbing enhancer-target relationships using high-throughput reporter assays and genome editing 2.
• Enhancer RNA biogenesis, function, and regulation are important for understanding how enhancers contribute to transcriptional activation, and dysregulation of eRNAs has been implicated in various diseases 6.