Comparative analysis of chromatin landscape in regulatory regions of human housekeeping and tissue specific genes

Abstract

Background: Global regulatory mechanisms involving chromatin assembly and remodelling in the promoter regions of genes is implicated in eukaryotic transcription control especially for genes subjected to spatial and temporal regulation. The potential to utilise global regulatory mechanisms for controlling gene expression might depend upon the architecture of the chromatin in and around the gene. In-silico analysis can yield important insights into this aspect, facilitating comparison of two or more classes of genes comprising of a large number of genes within each group.

Results: In the present study, we carried out a comparative analysis of chromatin characteristics in terms of the scaffold/matrix attachment regions, nucleosome formation potential and the occurrence of repetitive sequences, in the upstream regulatory regions of housekeeping and tissue specific genes. Our data show that putative scaffold/matrix attachment regions are more abundant and nucleosome formation potential is higher in the 5' regions of tissue specific genes as compared to the housekeeping genes.

Conclusion: The differences in the chromatin features between the two groups of genes indicate the involvement of chromatin organisation in the control of gene expression. The presence of global regulatory mechanisms mediated through chromatin organisation can decrease the burden of invoking gene specific regulators for maintenance of the active/silenced state of gene expression. This could partially explain the lower number of genes estimated in the human genome.

Figure 1

Nucleosome formation potential score distributions for 5' regions of housekeeping and tissue specific genes. The 5' sequences of human housekeeping and tissue specific genes were analysed by Recon for distribution of nucleosome formation potential scores. Frequency distribution histograms were plotted for scores in various intervals (range -3.2 to +3.2). (A) and (B) show the distribution of nucleosome formation potential scores at 400 and 2000 bp upstream from the gene start site respectively. Nucleosomal density is significantly lower for housekeeping genes as compared to tissue specific ones, in regions close to the gene start site.

Figure 2

Nucleosome formation potential score distributions for 5' regions at different positions from the gene start site in housekeeping and tissue specific genes. The 5' regions of 800, 1200 and 1600 bp from the gene start site of housekeeping and tissue specific genes were taken for the analysis. Frequency distribution histograms were plotted for Recon scores in various intervals (range -3.2 to +3.2). (A), (B) and (C) show the distribution of nucleosome formation potential scores at 800, 1200 and 1600 bp upstream from the gene start site respectively. As we move upstream from the gene start site, the difference in the nucleosome formation potentials between housekeeping and tissue specific genes gradually fades away.

Figure 3

A model for chromatin landscape in 5' regions of tissue specific and housekeeping genes. (A) depicts the repressive role of chromatin in maintaining tissue specific gene expression profiles in a chromosome. The chromatin organisation in the 5' regions of Tsg1 and Tsg2, two different tissue specific genes dispersed in the chromosome is shown. Nucleosome formation potentials and S/MARs – the boundary elements, are enriched in their upstream regions and might play a major role in facilitating tissue specific expression. This is likely to be a local effect since neighbouring genes might have a different expression pattern. (B) depicts the chromatin organisation in the 5' regions of Hkg1, Hkg2 and Hkg3, three housekeeping genes clustered in the chromosome. The presence of low nucleosome formation potential regions and enrichment of nucleosome destabilising elements ensure an open chromatin configuration in this domain. As Hkg generally cluster together, they are depleted in S/MARs relative to tissue specific genes as shown in the present analysis by the significant absence of predicted S/MARs in both 5' and 3' regions of housekeeping genes as compared to tissue specific genes.