Statistical-mechanical lattice models for protein-DNA binding in chromatin

TL;DR

This paper develops a theoretical framework for statistical-mechanical lattice models to describe protein-DNA interactions within chromatin, aiding understanding of gene regulation mechanisms.

Contribution

It introduces a new lattice model framework specifically for histone-DNA interactions in chromatin, extending existing models to include chromosomal proteins and transcription factors.

Findings

Model accurately describes histone-DNA binding in chromatin

Framework enables quantitative analysis of gene regulation

Applicable to genome-wide protein occupancy data

Abstract

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.