DNase-seq (
DNase I hypersensitive site
In genetics, DNase I hypersensitive sites (DHSs) 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 ac ...
s sequencing) is a method in
molecular biology
Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
used to identify the location of regulatory regions, based on the genome-wide sequencing of regions sensitive to cleavage by
DNase I
Deoxyribonuclease I (usually called DNase I), is an endonuclease of the DNase family coded by the human gene DNASE1.
DNase I is a nuclease that cleaves DNA preferentially at phosphodiester linkages adjacent to a pyrimidine nucleotide, yielding ...
.
FAIRE-Seq FAIRE-Seq (Formaldehyde-Assisted Isolation of Regulatory Elements) is a method in molecular biology used for determining the sequences of DNA regions in the genome associated with regulatory activity. The technique was developed in the laboratory of ...
is a successor of DNase-seq for the genome-wide identification of accessible DNA regions in the genome. Both the protocols for identifying open chromatin regions have biases depending on underlying nucleosome structure. For example, FAIRE-seq provides higher tag counts at non-promoter regions.
On the other hand, DNase-seq signal is higher at promoter regions, and DNase-seq has been shown to have better sensitivity than FAIRE-seq even at non-promoter regions.
DNase-seq Footprinting
DNase-seq requires some downstream bioinformatics analyses in order to provide genome-wide
DNA footprints. The computational tools proposed can be categorized in two classes: segmentation-based and site-centric approaches. Segmentation-based methods are based on the application of
Hidden Markov model
A hidden Markov model (HMM) is a statistical Markov model in which the system being modeled is assumed to be a Markov process — call it X — with unobservable ("''hidden''") states. As part of the definition, HMM requires that there be an ob ...
s or sliding window methods to segment the genome into open/closed chromatin region. Examples of such methods are: HINT,
Boyle method
and Neph method.
Site-centric methods, on the other hand, find footprints given the open chromatin profile around motif-predicted binding sites, i.e., regulatory regions predicted using DNA-protein sequence information (encoded in structures such as
Position weight matrix
A position weight matrix (PWM), also known as a position-specific weight matrix (PSWM) or position-specific scoring matrix (PSSM), is a commonly used representation of motifs (patterns) in biological sequences.
PWMs are often derived from a set ...
). Examples of these methods are CENTIPEDE
and Cuellar-Partida method.
References
{{Reflist
External links
DNase I footprinting analysis of DNase-seq data in R/BioconductorHINT : Tutorial for detection of DNAse footprints with HINT.
CENTIPEDE Website
Molecular biology techniques