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Evidence for the nuclear import of histones H3.1 & H4 as monomers
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Apta-Smith, Michael James, Hernandez Fernaud, Juan Ramon and Bowman, Andrew J. (2018) Evidence for the nuclear import of histones H3.1 & H4 as monomers. EMBO Journal, 37 (19). e98714. doi:10.15252/embj.201798714
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Official URL: http://dx.doi.org/10.15252/embj.201798714
Abstract
We present here evidence that histones H3.1 and H4 can be imported into the nucleus as monomers in human cells. Using a tether-and-release system to study the cytosolic phase and import dynamics of newly synthesised histones, we find that H3.1 and H4 can be maintained as stable monomers in the cytosol in a tethered state. Cytosolically tethered histones are bound tightly to Importin-b proteins (predominantly IPO4), but not to the histone specific chaperones NASP, ASF1a, RbAp46 (RBBP7) or HAT1, which reside in the nucleus in interphase cells. Release of monomeric histones from their cytosolic tether results in rapid nuclear translocation, dissociation with IPO4 and incorporation into chromatin at sites of replication. Quantitative analysis of histones bound to individual chaperones under steady-state conditions reveals an excess of H3 specifically associated with sNASP, suggesting that NASP can maintain a soluble, monomeric pool of H3 within the nucleus and may act as a nuclear receptor for newly imported histone. In summary, we propose that histones H3 and H4 are rapidly imported as monomeric units, forming heterodimers in the nucleus rather than the cytosol.
| Item Type: | Journal Article | |||||||||
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| Subjects: | Q Science > QH Natural history > QH426 Genetics | |||||||||
| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science > Life Sciences (2010- ) Faculty of Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Histones, Monomers, Cell division, Cytosol, Chromatin | |||||||||
| Journal or Publication Title: | EMBO Journal | |||||||||
| Publisher: | Nature Publishing Group | |||||||||
| ISSN: | 0261-4189 | |||||||||
| Official Date: | 1 October 2018 | |||||||||
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| Volume: | 37 | |||||||||
| Number: | 19 | |||||||||
| Article Number: | e98714 | |||||||||
| DOI: | 10.15252/embj.201798714 | |||||||||
| Status: | Peer Reviewed | |||||||||
| Publication Status: | Published | |||||||||
| Access rights to Published version: | Open Access | |||||||||
| Copyright Holders: | Andrew J Bowman | |||||||||
| RIOXX Funder/Project Grant: |
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