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Microinjection of Antibodies Targeting the Lamin A/C Histone-Binding Site Blocks Mitotic Entry and Reveals Separate Chromatin Interactions with HP1, CenpB and PML

The Wellcome Trust Centre for Cell Biology, University of Edinburgh, Kings Buildings, Swann 5.22, Max Born Crescent, Edinburgh EH9 3BF, UK
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Academic Editor: Thomas Dechat
Received: 16 January 2017 / Revised: 24 February 2017 / Accepted: 14 March 2017 / Published: 25 March 2017
(This article belongs to the Collection Lamins and Laminopathies)
Lamins form a scaffold lining the nucleus that binds chromatin and contributes to spatial genome organization; however, due to the many other functions of lamins, studies knocking out or altering the lamin polymer cannot clearly distinguish between direct and indirect effects. To overcome this obstacle, we specifically targeted the mapped histone-binding site of A/C lamins by microinjecting antibodies specific to this region predicting that this would make the genome more mobile. No increase in chromatin mobility was observed; however, interestingly, injected cells failed to go through mitosis, while control antibody-injected cells did. This effect was not due to crosslinking of the lamin polymer, as Fab fragments also blocked mitosis. The lack of genome mobility suggested other lamin-chromatin interactions. To determine what these might be, mini-lamin A constructs were expressed with or without the histone-binding site that assembled into independent intranuclear structures. HP1, CenpB and PML proteins accumulated at these structures for both constructs, indicating that other sites supporting chromatin interactions exist on lamin A. Together, these results indicate that lamin A-chromatin interactions are highly redundant and more diverse than generally acknowledged and highlight the importance of trying to experimentally separate their individual functions. View Full-Text
Keywords: lamin; cell cycle; genome stability; DNA replication; centromere proteins lamin; cell cycle; genome stability; DNA replication; centromere proteins
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Dixon, C.R.; Platani, M.; Makarov, A.A.; Schirmer, E.C. Microinjection of Antibodies Targeting the Lamin A/C Histone-Binding Site Blocks Mitotic Entry and Reveals Separate Chromatin Interactions with HP1, CenpB and PML. Cells 2017, 6, 9.

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