TY  - JOUR
AU  - Loi, M
AU  - Cenni, V
AU  - Duchi, S
AU  - Squarzoni, S
AU  - Lopez-Otin, C
AU  - Foisner, R
AU  - Lattanzi, G
AU  - Capanni, C
Y2  - 2020/12/21
Y1  - 2016/03/29
SN  - 1949-2553
UR  - http://hdl.handle.net/11343/256535
AB  - 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.
LA  - English
PB  - IMPACT JOURNALS LLC
T1  - Barrier-to-Autointegration Factor (BAF) involvement in prelamin A-related chromatin organization changes
DO  - 10.18632/oncotarget.6697
IS  - Oncotarget
VL  - 7
IS  - 13
SP  - 15662-15677
L1  - /bitstream/handle/11343/256535/PMC4941268.pdf?sequence=1&isAllowed=y
ER  -