5 research outputs found
Statistical-mechanical lattice models for protein-DNA binding in chromatin
Statistical-mechanical lattice models for protein-DNA binding are well
established as a method to describe complex ligand binding equilibriums
measured in vitro with purified DNA and protein components. Recently, a new
field of applications has opened up for this approach since it has become
possible to experimentally quantify genome-wide protein occupancies in relation
to the DNA sequence. In particular, the organization of the eukaryotic genome
by histone proteins into a nucleoprotein complex termed chromatin has been
recognized as a key parameter that controls the access of transcription factors
to the DNA sequence. New approaches have to be developed to derive statistical
mechanical lattice descriptions of chromatin-associated protein-DNA
interactions. Here, we present the theoretical framework for lattice models of
histone-DNA interactions in chromatin and investigate the (competitive) DNA
binding of other chromosomal proteins and transcription factors. The results
have a number of applications for quantitative models for the regulation of
gene expression.Comment: 19 pages, 7 figures, accepted author manuscript, to appear in J.
Phys.: Cond. Mat
Predicting nucleosome positions on the DNA: combining intrinsic sequence preferences and remodeler activities
Nucleosome positions on the DNA are determined by the intrinsic affinities of histone proteins to a given DNA sequence and by the ATP-dependent activities of chromatin remodeling complexes that can translocate nucleosomes with respect to the DNA. Here, we report a theoretical approach that takes into account both contributions. In the theoretical analysis two types of experiments have been considered: in vitro experiments with a single reconstituted nucleosome and in vivo genome-scale mapping of nucleosome positions. The effect of chromatin remodelers was described by iteratively redistributing the nucleosomes according to certain rules until a new steady state was reached. Three major classes of remodeler activities were identified: (i) the establishment of a regular nucleosome spacing in the vicinity of a strong positioning signal acting as a boundary, (ii) the enrichment/depletion of nucleosomes through amplification of intrinsic DNA-sequence-encoded signals and (iii) the removal of nucleosomes from high-affinity binding sites. From an analysis of data for nucleosome positions in resting and activated human CD4+ T cells [Schones et al., Cell 132, p. 887] it was concluded that the redistribution of a nucleosome map to a new state is greatly facilitated if the remodeler complex translocates the nucleosome with a preferred directionality
Nucleosomes in gene regulation: theoretical approaches
This work reviews current theoretical approaches of biophysics and
bioinformatics for the description of nucleosome arrangements in chromatin and
transcription factor binding to nucleosomal organized DNA. The role of
nucleosomes in gene regulation is discussed from molecular-mechanistic and
biological point of view. In addition to classical problems of this field,
actual questions of epigenetic regulation are discussed. The authors selected
for discussion what seem to be the most interesting concepts and hypotheses.
Mathematical approaches are described in a simplified language to attract
attention to the most important directions of this field