RT Journal Article SR Electronic T1 Mitotic chromosome condensation resets chromatin to maintain transcriptional homeostasis JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.05.11.491439 DO 10.1101/2022.05.11.491439 A1 Lucía Ramos-Alonso A1 Petter Holland A1 Stéphanie Le Gras A1 Xu Zhao A1 Bernard Jost A1 Magnar Bjørås A1 Yves Barral A1 Jorrit M. Enserink A1 Pierre Chymkowitch YR 2022 UL http://biorxiv.org/content/early/2022/05/11/2022.05.11.491439.abstract AB Mitotic entry correlates with the condensation of the chromosomes, remodeling of histone modifications, exclusion of transcription factors from DNA and the broad downregulation of transcription. However, whether mitotic condensation influences transcription in the subsequent interphase is unknown. Here, we show that preventing one chromosome to condense during mitosis causes it to fail resetting transcription. Rather it diverted the transcription machinery and underwent unscheduled initiation of gene expression. This caused the activation of inducible transcriptional programs, such as the GAL genes, even in absence of the relevant stimuli. Strikingly, aberrant gene expression persisted into the next interphase. Thus, our study identifies the maintenance of transcriptional homeostasis as an unexpected and yet unexplored function of mitotic chromosome condensation.One-Sentence Summary Mitotic chromatin condensation resets the transcriptome to protect cells from transcriptional drifting after anaphase.Competing Interest StatementThe authors have declared no competing interest.