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

Manuela Loi, Vittoria Cenni, Serena Duchi, Stefano Squarzoni, Carlos Lopez-Otin, Roland Foisner, Giovanna Lattanzi, Cristina Capanni

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)15662-15677
Number of pages16
JournalOncotarget
Volume7
Issue number13
DOIs
Publication statusPublished - Mar 29 2016

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Keywords

  • Barrier-to-autointegration factor
  • Chromatin
  • Hutchinson-gilford-progeria syndrome
  • Nestor-guillermo progeria
  • Prelamin A

ASJC Scopus subject areas

  • Oncology

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