DNase I hypersensitive site


In genetics, DNase I hypersensitive sites are regions of chromatin that are sensitive to cleavage by the DNase I enzyme. In these specific regions of the genome, chromatin has lost its condensed structure, exposing the DNA and making it accessible. This raises the availability of DNA to degradation by enzymes, such as DNase I. These accessible chromatin zones are functionally related to transcriptional activity, since this remodeled state is necessary for the binding of proteins such as transcription factors.
Since the discovery of DHSs 30 years ago, they have been used as markers of regulatory DNA regions. These regions have been shown to map many types of cis-regulatory elements including promoters, enhancers, insulators, silencers and locus control regions. A high-throughput measure of these regions is available through DNase-Seq.

Massive analysis

The ENCODE project proposes to map all of the DHSs in the human genome with the intention of cataloging human regulatory DNA.
DHSs mark transcriptionally active regions of the genome, where there will be cellular selectivity. So, they used 125 different human cell types. This way, using the massive sequencing technique, they obtained the DHSs profiles of every cellular type. Through an analysis of the data, they identified almost 2.9 million distinct DHSs. 34% were specific to each cell type, and only a small minority were detected in all cell types. Also, it was confirmed that only 5% of DHSs were found in TSS regions. The remaining 95% represented distal DHSs, divided in a uniform way between intronic and intergenic regions. The data gives an idea of the great complexity regulating the genetic expression in the human genome and the quantity of elements that control this regulation.
The high-resolution mapping of DHSs in the model plant Arabidopsis thaliana has been reported. Total 38,290 and 41,193 DHSs in leaf and flower tissues have been identified, respectively.

Regulatory DNA tools

The study of DHS profiles combined with other techniques allows analysis of regulatory DNA in humans:
The data obtained were validated with the chromosome conformation capture carbon copy technique. This technique is based in the physical association that exists between the promoter and the enhancers, determining the regions of chromatin that enter in contact in the promoter/enhancer connections.
It was confirmed that the majority of promoters were related with more than one enhancer, which indicates the existence of a complicated network of regulation for the immense majority of genes. Surprisingly, they also found that approximately half of the enhancers were found to be associated with more than one promoter. This discovery shows that the human cis-regulatory system is much more complicated than initially thought.
The number of distal cis-regulatory elements connected to a promoter is related to the quantitative average of the regulation complexity of a gene. In this way, it was determined that human genes with more interactions with distal DHSs, and with at least one more complex regulation, corresponded with those genes with functions in the immune system. This indicates that the complexly of cellular and environmental signals processed by the immune system is directly encoded in the cis-regulatory architecture of its constituent genes.

Database