Abstract
To maintain phenotypes of cell lineages, cells must 'remember' which genes were active before mitosis entry and transmit this information to their daughter cells so that expression patterns can be faithfully re-established in G1. This phenomenon is called gene bookmarking. However, during mitosis transcription ceases, most sequence-specific proteins dissociate from DNA and the chromatin is tightly compacted, making it difficult to understand how gene activity 'memory' is maintained through this stage of the cell cycle1,2. A feature of gene bookmarking is that in mitotic cells, the promoters of formerly active genes lack compaction, but how compaction of these regions is inhibited is unknown3,4. Here we show that during mitosis, TATA-binding protein (TBP), which remains bound to DNA during mitosis, recruits PP2A. TBP also interacts with condensin to allow efficient dephosphorylation and inactivation of condensin near these promoters to inhibit their compaction. Further, ChIP-on-chip data show that TBP is bound to many chromosomal sites during mitosis, and is higher in transcribed regions but low in regions containing pseudogenes and genes whose expression is tissue-restricted. These results suggest that TBP is involved not only in gene transcription during interphase but also in preserving the memory of gene activity through mitosis to daughter cells.
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Acknowledgements
We are very grateful to Sui Huang and Arnold Berk for their generous gifts of GFP–TBP and GST–TBP plasmids, respectively, and to lab members for insightful discussions. This research was supported by NIH grants to K.D.S. (GM61053 and GM64606).
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The study was directed and funded by K.D.S.; N.L.V performed the in vitro binding experiments between GST–TBP and in vitro translated CAP-G; H.X. performed all other experiments and K.D.S. wrote the paper.
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Xing, H., Vanderford, N. & Sarge, K. The TBP–PP2A mitotic complex bookmarks genes by preventing condensin action. Nat Cell Biol 10, 1318–1323 (2008). https://doi.org/10.1038/ncb1790
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DOI: https://doi.org/10.1038/ncb1790
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