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Barrier-to-Autointegration Factor (BAF) involvement in prelamin A-related chromatin organization changes.

Autori

Loi M, Cenni V, Duchi S, Squarzoni S, Lopez-Otin C, Foisner R, Lattanzi G, Capanni C.

Riferimenti

ONCOTARGET 7(13) 15662-15677, 2016

Autori CNR

CENNI, SQUARZONI, LATTANZI; CAPANNI

Moduli

Abstract

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.

Link all articolo

http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=6697&pubmed-linkout=1

Parole Chiave

Note

10.18632/oncotarget.6697

Indietro


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