Cohesins coordinate gene transcriptions of related function within Saccharomyces cerevisiae

Abstract

Cohesion factors pair together sister chromatids from early S-phase until anaphase onset. Numerous findings also establish an additional role in transcription. In humans, mutations in cohesion factors result in developmental abnormalities such as Cornelia de Lange, Roberts Syndrome/SC-Phocomelia, Rothman-Thompson Syndrome and others. While clinically relevant, a detailed study that links experimentally-defined cohesin defects to transcriptional changes remains lacking. Here, we report on the effects of cohesin inactivation during an early and discrete portion of the cell cycle. Even transient cohesin inactivation during the G1 portion of the cell cycle results in significant and reproducible changes in transcription. Surprisingly, over a third of the affected genes exhibit inter-related functions, suggesting that cohesin positioning along chromosomes evolved to coordinate gene expression. Prior studies indicate that defects in rRNA maturation/ribosome biogenesis produce developmental maladies in humans. Thus, the identification of genes critical for rRNA maturation in this study is of particular interest.

Figure 1

Heat map of all 30 loci identified by microarray as either up-regulated (top) or down-regulated (bottom) in response to transient cohesin inactivation. Pooled and common results for each of the three independent experiments are shown.

Figure 2

Schematic indicates affected loci, relative to DNA strand, and resulting change in transcription (up- vs down-regulation) upon transient cohesin inactivation.