title: Barrier-to-autointegration factor (BAF) involvement in prelamin A-related chromatin organization changes.
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.
authors.affiliation: CNR-National Research Council of Italy, Institute of Molecular Genetics, Unit of Bologna, 40136 Bologna, Italy.|Laboratory of Musculoskeletal Cell Biology, IOR, 40136 Bologna, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Loi
authors.affiliation: CNR-National Research Council of Italy, Institute of Molecular Genetics, Unit of Bologna, 40136 Bologna, Italy.|Laboratory of Musculoskeletal Cell Biology, IOR, 40136 Bologna, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Cenni
authors.affiliation: Osteoarticolar Regeneration Laboratory, Rizzoli Orthopaedic Institute, 40136 Bologna, Italy.|Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40123 Bologna, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Duchi
authors.affiliation: CNR-National Research Council of Italy, Institute of Molecular Genetics, Unit of Bologna, 40136 Bologna, Italy.|Laboratory of Musculoskeletal Cell Biology, IOR, 40136 Bologna, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Squarzoni
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical Faculty, Oviedo University, 33006 Oviedo, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopez-Otin
authors.affiliation: Max F. Perutz Laboratories, Medical University of Vienna, A-1030 Vienna, Austria.
authors.forename: Roland
authors.initials: R
authors.lastname: Foisner
authors.affiliation: CNR-National Research Council of Italy, Institute of Molecular Genetics, Unit of Bologna, 40136 Bologna, Italy.|Laboratory of Musculoskeletal Cell Biology, IOR, 40136 Bologna, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lattanzi
authors.affiliation: CNR-National Research Council of Italy, Institute of Molecular Genetics, Unit of Bologna, 40136 Bologna, Italy.|Laboratory of Musculoskeletal Cell Biology, IOR, 40136 Bologna, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Capanni
mesh_terms: D002843:Chromatin / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D034904:Lamin Type A / Q000378:metabolism*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011371:Progeria / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: C501959:BANF1 protein, human; D002843:Chromatin; D004268:DNA-Binding Proteins; D034904:Lamin Type A; D009687:Nuclear Proteins; C090764:prelamin A
keywords: Hutchinson-Gilford progeria syndrome; Nestor-Guillermo progeria; barrier-to-autointegration factor; chromatin; prelamin A