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Did you know how enhancers can have amazing effects at remote locations in genes?
In genetics, an enhancer is a short (50-1500 bp) DNA sequence that can be bound by a protein (activator) to increase the likelihood that a specific gene will be transcribed. These proteins are often called transcription factors. Enhancers are cis-acting, which means they can be located upstream or downstream of a gene at a distance of up to 1 Mbp (1,000,000 bp). There are hundreds of thousands of enhancers in the human genome, and these enhancers are found not only in eukaryotes but also in prokaryotes. Their existence and functions are gradually being revealed by the scientific community, and they are particularly important in disease research and the regulation of gene expression.
Enhancers not only exert effects near genes, but can even activate the transcription of related genes through spatial interactions at distant locations.
The enhancer was first discovered in 1983 in the immunoglobulin heavy chain gene. It is located in a large intron, explaining the mechanism of transcriptional activation of the rearranged Vh gene promoter. And in recent years, studies of enhancers have shown that they play an important role in certain medical conditions, such as bone marrow suppression. What is most noteworthy is that starting in 2022, scientists will use artificial intelligence to design synthetic enhancers and apply them to animal systems to demonstrate their potential in innovative research.
Structure and function of enhancers
In eukaryotic cells, the chromatin structure of DNA is folded into a supercoiled state that mimics prokaryotic DNA. Although the DNA of the enhancer may be linearly far away from the gene, it is spatially close to the promoter and gene. This allows it to interact with general transcription factors and RNA polymerase II.
Enhancers not only promote gene expression, but some enhancers can also function on non-adjacent chromosomes.
Intriguingly, enhancers may be located upstream or downstream of a gene, and these enhancers do not need to be close to the transcription start site to affect transcription. Many studies have clearly shown that the activation of enhancers is closely related to the binding of specific transcription factors, and the presence and activity of these transcription factors directly affect the expression of target genes.
The role of enhancers in gene expression
In mammals, gene expression is regulated by a variety of homeopathic regulatory elements, including core promoters and promoters located near the start site of gene transcription. Although core promoters are capable of directing the initiation of transcription, they generally have low basal activity. In contrast, enhancers can significantly affect gene expression at distant locations, and activated enhancers can even increase gene expression to more than 100-fold levels.
The presence of enhancers allows specific gene expression to exhibit different patterns depending on different cell types and environments.
In specific tissue types, enhancers are closely connected to the promoters they regulate, forming a "loop" structure to promote gene expression. This mechanism has been confirmed in many nerve cells and tissues.
The evolution and examples of enhancers
Enhancers can also play a key role in evolution. Taking HACNS1 as an example, this enhancer may have promoted the evolution of the human thumb, while the GADD45G enhancer has different effects on brain development in different species. Changes in these enhancers provide new insights into biological evolution.
Understanding enhancer function and interactions is critical to solving many mysteries in developmental biology.
In developmental biology, enhancers serve as cis-regulatory elements to precisely regulate gene expression, and their effects affect cell development, differentiation and growth.
Future research directions
With the rapid development of genomics and epigenomics technologies, researchers have begun to use high-throughput technologies to identify and characterize these key cis-regulatory modules (CRMs). However, in comparative genomics, the fact that many enhancer functions can be accomplished without major sequence conservation, even when compared to sequences from many species, is particularly worthy of further investigation.
The application of these new technologies provides unprecedented opportunities for the discovery and functional understanding of enhancers.
In the future, as gene editing technology further develops, the ability to rewrite or correct enhancers will allow us to make significant progress in treating genetic diseases and developing new therapies. But whether we can fully grasp the role of these enhancers in biological adaptation and evolution is still an issue that needs to be explored urgently in science?
