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.
- Robert Tjian
- Sheila S Teves
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Karen Adelman, Harvard Medical School, United States
- Received: October 11, 2016
- Accepted: November 16, 2016
- Accepted Manuscript published: November 18, 2016 (version 1)
- Accepted Manuscript updated: November 21, 2016 (version 2)
- Accepted Manuscript updated: November 30, 2016 (version 3)
- Version of Record published: December 14, 2016 (version 4)
- Version of Record updated: December 16, 2016 (version 5)
© 2016, Teves et al.
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.
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