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

Sheila S Teves,Aarohi Bhargava-Shah,Robert Tjian,Luye An,Liangqi Xie,Xavier Darzacq

doi:10.7554/elife.35621

Sheila S Teves, Aarohi Bhargava-Shah + Show 4 more

Open Access

https://doi.org/10.7554/elife.35621

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Journal: eLife	Publication Date: Jun 25, 2018
Citations: 99	License type: CC BY 4.0

Affiliation: University of California, Berkeley, Cornell University

Abstract

Maintenance of transcription programs is challenged during mitosis when chromatin becomes condensed and transcription is silenced. How do the daughter cells re-establish the original transcription program? Here, we report that the TATA-binding protein (TBP), a key component of the core transcriptional machinery, remains bound globally to active promoters in mouse embryonic stem cells during mitosis. Using live-cell single-molecule imaging, we observed that TBP mitotic binding is highly stable, with an average residence time of minutes, in stark contrast to typical TFs with residence times of seconds. To test the functional effect of mitotic TBP binding, we used a drug-inducible degron system and found that TBP promotes the association of RNA Polymerase II with mitotic chromosomes, and facilitates transcriptional reactivation following mitosis. These results suggest that the core transcriptional machinery promotes efficient transcription maintenance globally.

Highlights

The cell cycle presents a challenge to maintenance of transcription programs
We have shown that unlike most classical transcription factors that bind with rapid dynamics, the endogenous TATA-binding protein (TBP) maintains stable binding at the transcription start sites (TSSs) of active genes in mitotic mouse embryonic stem cells (mESCs)
Such stable TBP binding leads to recruitment of Polymerase II (Pol II) to mitotic chromosomes, despite a global decrease in transcriptional activity

Summary

Introduction

The cell cycle presents a challenge to maintenance of transcription programs. The observation that DNase I hypersensitive sites were maintained in mitotic chromosomes (Martınez-Balbas et al, 1995) led to the theory of ‘mitotic bookmarking’ (Michelotti et al, 1997) where a select group of TFs maintain the ability to bind to target sequences during mitosis and ‘bookmark’ target genes for efficient reactivation. The first few TFs identified to bind to mitotic chromosomes provided early support for the bookmarking theory (Caravaca et al, 2013; Kadauke et al, 2012; Xing et al, 2005). Rather than acting as a stable bookmark, TFs seem to ‘hover’ on mitotic chromosomes.

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