Reference : HDAC5 is required for maintenance of pericentric heterochromatin, and controls cell-cycl...
Scientific journals : Article
Human health sciences : Oncology
http://hdl.handle.net/2268/113104
HDAC5 is required for maintenance of pericentric heterochromatin, and controls cell-cycle progression and survival of human cancer cells
English
Peixoto, Paul mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
Castronovo, Vincenzo mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire >]
Matheus, Nicolas [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
Polese, Catherine [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire >]
Peulen, Olivier mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques >]
Gonzalez, Arnaud mailto [Université de Liège - ULg > > > Form. doc. sc. bioméd. & pharma.]
Boxus, Mathieu mailto [Université de Liège - ULg > Chimie et bio-industries > Biologie cell. et moléc. >]
Verdin, Eric [University of California, San Francisco > Gladstone Institute of Virology and Immunology > > >]
Thiry, Marc mailto [Université de Liège - ULg > Département des sciences de la vie > Biologie cellulaire >]
Dequiedt, Franck mailto [Université de Liège - ULg > > GIGA-Research >]
Mottet, Denis mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
2012
Cell Death & Differentiation
Nature Publishing Group
Yes (verified by ORBi)
International
1350-9047
London
United Kingdom
[en] histone deacetylase ; cancer cells ; siRNA ; autophagy ; cell proliferation ; chemotherapy
[en] Histone deacetylases (HDACs) form a family of enzymes, which have fundamental roles in the epigenetic regulation of gene expression and contribute to the growth, differentiation, and apoptosis of cancer cells. In this study, we further investigated the biological function of HDAC5 in cancer cells. We found HDAC5 is associated with actively replicating pericentric heterochromatin during late S phase. We demonstrated that specific depletion of HDAC5 by RNA interference resulted in profound changes in the heterochromatin structure and slowed down ongoing replication forks. This defect in heterochromatin maintenance and assembly are sensed by DNA damage checkpoint pathways, which triggered cancer cells to autophagy and apoptosis, and arrested their growth both in vitro and in vivo. Finally, we also demonstrated that HDAC5 depletion led to enhanced sensitivity of DNA to DNA-damaging agents, suggesting that heterochromatin de-condensation induced by histone HDAC5 silencing may enhance the efficacy of cytotoxic agents that act by targeting DNA in vitro. Together, these results highlighted for the first time an unrecognized link between HDAC5 and the maintenance/assembly of heterochromatin structure, and demonstrated that its specific inhibition might contribute to increase the efficacy of DNA alteration-based cancer therapies in clinic.
Giga-Cancer
Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS ; Centre anti-cancéreux près de l'ULg ; Fonds Léon Fredericq ; Télévie
Researchers ; Professionals
http://hdl.handle.net/2268/113104
10.1038/cdd.2012.3

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