A dynamic mode of mitotic bookmarking by transcription factors

Abstract
Data availability
Article and author information
Metrics

Abstract

During mitosis, transcription is shut off, chromatin condenses, and most transcription factors (TFs) are reported to be excluded from chromosomes. How do daughter cells re-establish the original transcription program? Recent discoveries that a select set of TFs remain bound on mitotic chromosomes suggest a potential mechanism for maintaining transcriptional programs through the cell cycle termed mitotic bookmarking. Here we report instead that many TFs remain associated with chromosomes in mouse embryonic stem cells, and that the exclusion previously described is largely a fixation artifact. In particular, most TFs we tested are significantly enriched on mitotic chromosomes. Studies with Sox2 reveal that this mitotic interaction is more dynamic than in interphase and is facilitated by both DNA binding and nuclear import. Furthermore, this dynamic mode results from lack of transcriptional activation rather than decreased accessibility of underlying DNA sequences in mitosis. The nature of the cross-linking artifact prompts careful re-examination of the role of TFs in mitotic bookmarking.

Data availability

The following data sets were generated

1. Sheila Teves
(2016) Global accessibility of mitotic chromosomes
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE85184).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE85184

The following previously published data sets were used

1. Wei C
(2008) Mapping of transcription factor binding sites in mouse embryonic stem cells
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE11431).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE11431

Article and author information

Author details

Sheila S Teves

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-1220-2414
Luye An

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
No competing interests declared.
Anders S Hansen

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
No competing interests declared.
Liangqi Xie

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
No competing interests declared.
Xavier Darzacq

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
No competing interests declared.
Robert Tjian

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

For correspondence
jmlim@berkeley.edu

Competing interests
Robert Tjian, President of the Howard Hughes Medical Institute (2009-present), one of the three founding funders of eLife, and a member of eLife's Board of Directors.

"This ORCID iD identifies the author of this article:" 0000-0003-0539-8217

Funding

Howard Hughes Medical Institute

Robert Tjian

Jane Coffin Childs Memorial Fund for Medical Research

Sheila S Teves

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.