Chromatin regulators as capacitors of interspecies variations in gene expression

Gene expression varies widely between closely related species and strains, yet the genetic basis of most differences is still unknown. Several studies suggested that chromatin regulators have a key role in generating expression diversity, predicting a reduction in the interspecies differences on deletion of genes that influence chromatin structure or modifications. To examine this, we compared the genome‐wide expression profiles of two closely related yeast species following the individual deletions of eight chromatin regulators and one transcription factor. In all cases, regulator deletions increased, rather than decreased, the expression differences between the species, revealing hidden genetic variability that was masked in the wild‐type backgrounds. This effect was not observed for individual deletions of 11 enzymes involved in central metabolic pathways. The buffered variations were associated with trans differences, as revealed by allele‐specific profiling of the interspecific hybrids. Our results support the idea that regulatory proteins serve as capacitors that buffer gene expression against hidden genetic variability. Synopsis Biological systems are often robust to mutations—their outputs, (for example, gene expression profiles) remain stable in the face of mutations. This ensures that most individuals maintain the ‘correct’ behavior, which has been shaped by million of years of evolution, despite a constant flux of mutations. How is robustness maintained, and in particular, which genes are required for it? Such questions have been studied for decades, yet there are no simple answers. Previous studies suggested that particular proteins, termed genetic capacitors, buffer the effects of mutations, thereby promoting robustness. The classical example of such a protein is Hsp90, whose activity as a chaperone has been proposed to aid the correct folding of mutant proteins and thus buffer the structural effects of mutations. The hallmark of a genetic capacitor is that its deletion reveals phenotypic differences between individuals or species, which are hidden (that is, buffered) in its presence. The example of Hsp90 may suggest that buffering is a property of only few proteins that carry particular catalytic functions such as chaperones. However, theoretical studies have instead suggested that many proteins serve as genetic capacitors and that buffering is not necessarily a consequence of their direct activity but rather emerges naturally during evolutio