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Oncotarget. 2016 Mar 29;7(13):15662-77. doi: 10.18632/oncotarget.6697.

Barrier-to-autointegration factor (BAF) involvement in prelamin A-related chromatin organization changes.

Author information

1
CNR-National Research Council of Italy, Institute of Molecular Genetics, Unit of Bologna, 40136 Bologna, Italy.
2
Laboratory of Musculoskeletal Cell Biology, IOR, 40136 Bologna, Italy.
3
Osteoarticolar Regeneration Laboratory, Rizzoli Orthopaedic Institute, 40136 Bologna, Italy.
4
Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40123 Bologna, Italy.
5
Department of Biochemistry and Molecular Biology, Medical Faculty, Oviedo University, 33006 Oviedo, Spain.
6
Max F. Perutz Laboratories, Medical University of Vienna, A-1030 Vienna, Austria.

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.

KEYWORDS:

Hutchinson-Gilford progeria syndrome; Nestor-Guillermo progeria; barrier-to-autointegration factor; chromatin; prelamin A

PMID:
26701887
PMCID:
PMC4941268
DOI:
10.18632/oncotarget.6697
[Indexed for MEDLINE]
Free PMC Article

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