A Statistical–Mechanical Model for Regulation of Long-range Chromatin Structure and Gene Expression

In eukaryotic organisms, organization of chromatin is considered to play a role in transcriptional regulation by limiting the accessibility of a gene to the transcription machinery. It is not fully understood, however, how chromatin around a particular locus can be specifically altered to allow transcription. This paper introduces a statistical–mechanical model of chromatin to illustrate a potential mechanism. The model, which is mathematically equivalent to the one-dimensional Ising model of magnetic systems, explains how gene regulatory DNA sequences can affect the chromatin structure over a long distance in cis. The main assumption of the model is cooperativity of histone H1 in binding to the nucleosome array. This cooperativity results in a long-range correlation of histone H1 distribution along the chromatin. Due to this long-range correlation, a gene regulatory element, such as a transcriptional enhancer, may lead to depletion of histone H1 over a large region of chromatin thereby increasing the accessibility of the gene. The model provides a mechanism for a sensitive genetic switch and explains several aspects of gene regulation and chromatin structure.