An enhancer is a cis-regulatory DNA element that increases the transcription of associated genes, often functioning at a distance from the gene it regulates. Unlike promoters, which are located immediately upstream of genes, enhancers can be located upstream, downstream, or even within introns of their target genes.
### Key Characteristics of Enhancers 1. Distance-Independent Action – Enhancers can function kilobases to megabases away from the genes they regulate. 2. Orientation Independence – They can work in both forward and reverse orientations. 3. Tissue-Specific and Developmental Regulation – Enhancer activity varies across different cell types, tissues, and developmental stages. 4. Binding Sites for Transcription Factors (TFs) – Enhancers contain multiple binding sites for TFs that help recruit the transcriptional machinery to the promoter of the target gene. 5. Chromatin Accessibility – Enhancers are often found in open chromatin regions, marked by histone modifications like H3K27ac (active enhancers) and H3K4me1 (primed enhancers).
### How Enhancers Work - Transcription Factor Binding: Enhancers bind TFs, which recruit co-activators and the basal transcription machinery. - Chromatin Looping: Enhancers interact with promoters through chromatin looping, bringing regulatory elements into close proximity. - Mediator and Cohesin Complexes: These protein complexes help facilitate the interaction between enhancers and promoters.
### Types of Enhancers 1. Constitutive Enhancers – Active in multiple cell types. 2. Cell-Type Specific Enhancers – Only active in certain tissues or conditions. 3. Super-Enhancers – Clusters of highly active enhancers that drive high expression of key genes, often associated with cell identity and disease states like cancer.
### Enhancers and Disease - Mutations or dysregulation of enhancers can lead to misexpression of genes, contributing to diseases such as: