By co-immunoprecipitation experiments and in situ proximity ligation assay, we determined a molecular interaction between HDAC2 and lamin A/C. Lamin A/C binds HDAC2 both in its native and in its phosphorylated form. Binding is increased by TSA and MC1568, which inhibits class II HDACs, indicating that lamin A/C preferentially binds HDAC2 upon inhibition of class II HDACs. Moreover, lamin A/C binds the HDAC2 substrate acetyl-H4K16 and the interaction is released upon TSA treatment, suggesting that lamin A/C binding to HDAC2 in the histone-containing platform is aimed at release of HDAC2 from nucleosomes and recruitment to the nuclear lamina. These data were supported by the accumulation of lamin A/C-bound HDAC2 at the nuclear periphery upon enzyme inhibition. Under oxidative stress conditions, lamin A/C-HDAC2 binding was reduced and confined at the nuclear periphery, in agreement with the reduced HDAC2 activity at the late stages of DNA damage response. Moreover, histone acetylation was increased at late stages of DNA damage response and lamin A/C-HDAC2 binding was restored upon DNA damage recovery. These results show that lamin A/C contributes to genome maintenance by modulation of HDAC2 recruitment during oxidative stress response.
Lamin A/C-HDAC2 interplay during oxidative stress response
E Mattioli;D Andrenacci;G Lattanzi
2015
Abstract
By co-immunoprecipitation experiments and in situ proximity ligation assay, we determined a molecular interaction between HDAC2 and lamin A/C. Lamin A/C binds HDAC2 both in its native and in its phosphorylated form. Binding is increased by TSA and MC1568, which inhibits class II HDACs, indicating that lamin A/C preferentially binds HDAC2 upon inhibition of class II HDACs. Moreover, lamin A/C binds the HDAC2 substrate acetyl-H4K16 and the interaction is released upon TSA treatment, suggesting that lamin A/C binding to HDAC2 in the histone-containing platform is aimed at release of HDAC2 from nucleosomes and recruitment to the nuclear lamina. These data were supported by the accumulation of lamin A/C-bound HDAC2 at the nuclear periphery upon enzyme inhibition. Under oxidative stress conditions, lamin A/C-HDAC2 binding was reduced and confined at the nuclear periphery, in agreement with the reduced HDAC2 activity at the late stages of DNA damage response. Moreover, histone acetylation was increased at late stages of DNA damage response and lamin A/C-HDAC2 binding was restored upon DNA damage recovery. These results show that lamin A/C contributes to genome maintenance by modulation of HDAC2 recruitment during oxidative stress response.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
