Barrier-to-Autointegration Factor (BAF) involvement in prelamin A-related chromatin organization changes
Web of Science
AuthorLoi, M; Cenni, V; Duchi, S; Squarzoni, S; Lopez-Otin, C; Foisner, R; Lattanzi, G; Capanni, C
PublisherIMPACT JOURNALS LLC
University of Melbourne Author/sDuchi, Serena
AffiliationSurgery (St Vincent's)
Document TypeJournal Article
CitationsLoi, M., Cenni, V., Duchi, S., Squarzoni, S., Lopez-Otin, C., Foisner, R., Lattanzi, G. & Capanni, C. (2016). Barrier-to-Autointegration Factor (BAF) involvement in prelamin A-related chromatin organization changes. ONCOTARGET, 7 (13), pp.15662-15677. https://doi.org/10.18632/oncotarget.6697.
Access StatusOpen Access
Chromatin disorganization is one of the major alterations linked to prelamin A processing impairment. In this study we demonstrate that BAF is necessary to modulate prelamin A effects on chromatin structure. We show that when prelamin A and BAF cannot properly interact no prelamin A-dependent effects on chromatin occur; similar to what is observed in human Nestor Guillermo Progeria Syndrome cells harboring a BAF mutation, in HEK293 cells expressing a BAF mutant unable to bind prelamin A, or in siRNA mediated BAF-depleted HEK293 cells expressing prelamin A. BAF is necessary to induce histone trimethyl-H3K9 as well as HP1-alpha and LAP2-alpha nuclear relocalization in response to prelamin A accumulation. These findings are enforced by electron microscopy evaluations showing how the prelamin A-BAF interaction governs overall chromatin organization. Finally, we demonstrate that the LAP2-alpha nuclear localization defect observed in HGPS cells involves the progerin-BAF interaction, thus establishing a functional link between BAF and prelamin A pathological forms.
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