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. 2012 May-Jun;3(3):213-9.
doi: 10.4161/nucl.19513. Epub 2012 May 1.

The discrepancy between chromatin factor location and effect

Tineke L Lenstra  1 , Frank C P Holstege
Affiliations

The discrepancy between chromatin factor location and effect

Tineke L Lenstra et al. Nucleus. 2012 May-Jun.

Abstract

The influence of chromatin on many cellular processes is well appreciated. Much has been learned by studying the role of chromatin remodeling and modifying complexes on individual genes. The seemingly straightforward models that inevitably arise from such studies are challenged by genome-wide analyses. Two recent studies in Saccharomyces cerevisiae provide unprecedented coverage of both the genome-wide location and the effect on gene expression for the majority of chromatin factors. Comparison of the overlap between location and expression effects reveals a large disconnect, with on average only 2.5% of occupied genes showing changes in expression. It is also interesting that only 24% of all expression effects are associated with chromatin factor occupancy. The large difference between location and effect likely reflects general properties inherent to regulation of gene expression through chromatin in yeast. Explanations for the discrepancy include gene-specific properties that exert a requirement for certain factors only on specific genes, as well as functional redundancy, whereby loss of a particular factor is compensated by others that function in a distinct but nevertheless compensatory manner. Since the majority of chromatin factor perturbations do show significant effects on specific subsets of genes, this implies the presence of different types of gene-specific properties that determine which chromatin factors a particular gene requires for proper expression. Understanding these gene-specific properties should be the focus of future studies aimed at understanding regulation of gene expression through chromatin.

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Figures

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Figure 1. (A) Correlation analysis between occupancy and expression values for 70 chromatin regulators. For the 70 chromatin regulators that overlap between the location and expression data sets, the uncentered cosine correlation (R) is shown between occupancy values at the promoter (maximum value of UAS and TSS probe) and mRNA expression changes upon deletion. The correlation is based on the 5,482 genes shared between the 2 data sets. Correlation values marked by a star (*) indicate significant correlations (p < 0.01, after Bonferroni multiple testing correction). (B) Correlation plots of promoter occupancy (x-axis) and expression (y-axis) for the highest positive (Ssn6) and highest negative (Htz1) correlation.
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Figure 2. Overlap between occupancy and expression. (A) Venn diagram of overlap between binding targets (5% FDR) and expression effects (fold change > 1.7, p < 0.05) for all overlapping factors. (B) Number of significant up and downregulated genes for deletion mutants of the factors shown on the x-axis. Genes that are also bound by the same factor are colored dark gray. Bars marked by a star (*) show significant overlap between binding and up or downregulated genes (hypergeometric test, p < 0.01). (C) Number of genes occupied by the factors shown on the x-axis. Genes that also show expression effects in the corresponding deletion mutants are colored yellow (upregulation) or blue (downregulation). Yellow and blue stars indicate significant overlap between occupancy and up or downregulated genes, respectively (hypergeometric test, p < 0.01). (D) The fractions bound/changed and changed/bound are plotted for the upregulated genes (yellow dots) and downregulated genes (blue dots) separately.
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Comment on

  • Lenstra TL, Benschop JJ, Kim T, Schulze JM, Brabers NA, Margaritis T, et al. The specificity and topology of chromatin interaction pathways in yeast. Mol Cell. 2011;42:536–49. doi: 10.1016/j.molcel.2011.03.026.

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