Transcriptional Output Transiently Spikes Upon Mitotic Exit

Abstract

The pulsatile nature of gene activity has recently emerged as a general property of the transcriptional process. It has been shown that the frequency and amplitude of transcriptional bursts can be subjected to extrinsic regulation. Here we have investigated if these parameters were constant throughout the cell cycle using the single molecule RNA FISH technique. We found evidence of transcriptional spikes upon mitotic exit in three different human cell lines. Recording of cell growth prior to hybridization and immuno-RNA FISH analysis revealed that these spikes were short-lived and subsided before completion of cytokinesis. The transient post-mitotic increase in transcriptional output was found to be the result of cells displaying a higher number of active alleles and/or an increased number of nascent transcripts per active allele, indicating that both the burst fraction and the amplitude of individual bursts can be increased upon mitotic exit. Our results further suggest that distinct regulatory mechanisms are at work shortly after mitotic exit and during the rest of interphase. We speculate that transcriptional spikes are associated with chromatin decondensation, a hallmark of post-mitotic cells that might alter the dynamics of transcriptional regulators and effectors.

A changing paradigm of transcriptional memory propagation through mitosis

“…The authors thus concluded that transcription is globally reactivated in a large burst, during which transcript levels temporarily exceed that in interphase before decreasing back to interphase levels. This discovery of a ‘spike’ in transcription amplitude during mitotic exit was also found in three additional cell types by single-molecule RNA FISH 61 . Again, after the initial burst, the transcript levels subsided shortly after, before cytokinesis.…”

A stable mode of bookmarking by TBP recruits RNA Polymerase II to mitotic chromosomes

“…Recent studies, however, are beginning to shed some nuance to this historical adage. For instance, several groups have shown that transcription transiently spikes at the later stages of mitosis, followed by an adjustment back to normal interphase levels (43,44). One potential mechanism for such a spike in transcriptional activity could derive from our observed recruitment of Pol II by TBP to mitotic chromosomes.…”

A stable mode of bookmarking by TBP recruits RNA polymerase II to mitotic chromosomes

“…Recent studies, however, are beginning to shed some nuance to this historical adage. For instance, several groups have shown that transcription transiently spikes at the later stages of mitosis, followed by an adjustment back to normal interphase levels ( Hsiung et al, 2016 ; Vaňková Hausnerová and Lanctôt, 2017 ). One potential mechanism for such a spike in transcriptional activity could derive from our observed recruitment of Pol II by TBP to mitotic chromosomes.…”