title: A dynamic mode of mitotic bookmarking by transcription factors.
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.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, United States.
authors.forename: Sheila S
authors.identifier: 0000-0002-1220-2414
authors.initials: SS
authors.lastname: Teves
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, United States.
authors.forename: Luye
authors.initials: L
authors.lastname: An
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, United States.|CIRM Center of Excellence, University of California, Berkeley, Berkeley, United States.
authors.forename: Anders S
authors.initials: AS
authors.lastname: Hansen
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, United States.|CIRM Center of Excellence, University of California, Berkeley, Berkeley, United States.
authors.forename: Liangqi
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, United States.|CIRM Center of Excellence, University of California, Berkeley, Berkeley, United States.
authors.forename: Xavier
authors.initials: X
authors.lastname: Darzacq
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, United States.|CIRM Center of Excellence, University of California, Berkeley, Berkeley, United States.|Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States.
authors.forename: Robert
authors.identifier: 0000-0003-0539-8217
authors.initials: R
authors.lastname: Tjian
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002875:Chromosomes / Q000737:chemistry*; D051379:Mice; D008938:Mitosis; D000066450:Mouse Embryonic Stem Cells / Q000502:physiology*; D014157:Transcription Factors / Q000032:analysis*; D014158:Transcription, Genetic
chemical_list: D014157:Transcription Factors
keywords: cell biology; chromosomes; embryonic stem cells; genes; knock-in cells; mouse