Mitotic chromosome condensation resets chromatin to maintain post-anaphase transcriptional homeostasis (RNA-Seq I)

Mitotic entry correlates with remodeling of histone modifications, chromatin condensation, exclusion of transcription factors from the DNA and broad downregulation of transcription. However, whether mitotic condensation also influences interphase transcription is a question that has not been addressed yet. In this study, we reveal that loss of mitotic chromatin condensation results in a dramatic and spontaneous recruitment of the transcription machinery and unscheduled initiation of gene expression. This includes activation of inducible transcriptional programs, which occurs even in absence of relevant stimuli, such as the GAL system. Strikingly, such an erratic gene expression goes on after exit from mitosis. Thus, we reveal a novel function of mitotic chromosome condensation, i.e. resetting the transcriptome to prevent gene expression from drifting and maintain transcriptional homeostasis during interphase. Overall design: RNAseq time-course experiment in CEN4 and CEN4* cells at 0, 30, 60, 120 and 180 minutes after the addition of beta-estradiol. Three independent experiments, total of 30 samples. In the CEN4 control strain, the centromere of Chromosome IV is not flaked with lox site. When the centromere of chromosome IV is flanked by lox recombination sites, it is referred to as CEN4* before excision and cen4- after excision by the Cre recombinase.