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Posts Tagged ‘statistical model’


Author and Reporter: Anamika Sarkar, Ph.D

In Eukaryotic cells, a compact structure of histones, which facilitates chromosomal DNA to be folded inside nucleus are called nucleosomes (Fig. 1). In each nucleosome, histone octamers, which have diameter of 10nm are wrapped around by 147 base pairs of DNA. The positioning of nucleosomes has been proven to be important criteria for downstream activation of signals.

 Image

Figure 1: Nucleosome Structure

The mathematical models which have been developed to describe position of single histone octamers on DNA as a function of DNA sequences can be divided into two types. One is based on structural parameters obtained from crystal structures while the second one is based on the probability of distribution of dinucleotides which are found in natively assembled chromatin. However, none of these approaches was able to match their modeling results with experimental results which are based on well defined substrates in vitro and in vivo assembled chromatin.

Heijden et. al. in  a recent paper (Proc Natl Acad Sci U S A. 2012, Aug 20 [Epub ahead of print]) developed a nucelosome positioning model based on periodic probability function of distribution of dinucleotides TA, TT, AA and GC. Their model is a simple mathematical model of finding the probability of nucleosome dyads, where histones are known to localize. Their model can be described by three parameters – amplitude, period and length of each dinucleotide. Their model results were then mapped to sequence specific energy landscape for nucleosome binding. Their predicted results of relative nucleosome affinities showed higher accuracy when compared with experimental results.

The authors’ model of connecting nucleosome positions with free energy landscapes is a step forward towards understanding importance of DNA availability or non availability for downstream signaling events. The importance of ATP (Adenosine-5′-triphosphate) as energy currency for any cellular events have already been realized. Now it will be possible to connect the dots in understanding availability of ATPs for different biological processes at nucelosome levels by proper extensions of Heijden et. al.

Sources:

Heijden et. al. article:  http://www.ncbi.nlm.nih.gov/pubmed/22908247

Nucleosome Structure: http://click4biology.info/c4b/7/pro7.1.htm

Nucleosome and DNA structure video : http://www.youtube.com/watch?v=gbSIBhFwQ4s

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