Statins and Histone Deacetylase Inhibitors Affect Lamin A/C - Histone Deacetylase 2 Interaction in Human Cells

Elisabetta Mattioli, Davide Andrenacci, Antonello Mai, Sergio Valente, Joke Robijns, Winnok H De Vos, Cristina Capanni, Giovanna Lattanzi

Research output: Contribution to journalArticlepeer-review

Abstract

We recently identified lamin A/C as a docking molecule for human histone deacetylase 2 (HDAC2) and showed involvement of HDAC2-lamin A/C complexes in the DNA damage response. We further showed that lamin A/C-HDAC2 interaction is altered in Hutchinson-Gilford Progeria syndrome and other progeroid laminopathies. Here, we show that both inhibitors of lamin A maturation and small molecules inhibiting HDAC activity affect lamin A/C interaction with HDAC2. While statins, which inhibit prelamin A processing, reduce protein interaction, HDAC inhibitors strengthen protein binding. Moreover, treatment with HDAC inhibitors restored the enfeebled lamin A/C-HDAC2 interaction observed in HGPS cells. Based on these results, we propose that prelamin A levels as well as HDAC2 activation status might influence the extent of HDAC2 recruitment to the lamin A/C-containing platform and contribute to modulate HDAC2 activity. Our study links prelamin A processing to HDAC2 regulation and provides new insights into the effect of statins and histone deacetylase inhibitors on lamin A/C functionality in normal and progeroid cells.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalFrontiers in Cell and Developmental Biology
Volume7
DOIs
Publication statusPublished - Jan 31 2019

Keywords

  • HDAC inhibitors
  • HDAC2
  • LMNA gene
  • chromatin
  • prelamin A
  • statins
  • trichostatin A (TSA)

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