The effects of histone deacetylase inhibitors on heterochromatin: implications for anticancer therapy?
Histone acetylation regulates many chromosome functions, such as gene expression and chromosome segregation. Histone deacetylase inhibitors (HDACIs) induce growth arrest, differentiation and apoptosis of cancer cells ex vivo, as well as in vivo in tumour-bearing animal models, and are now undergoing clinical trials as anti-tumour agents. However, little attention has been paid to how HDACIs function in these biological settings and why different cells respond in different ways. Here, we discuss the consequences of inhibiting histone deacetylases in cycling versus non-cycling cells, in light of the dynamics of histone acetylation patterns with a specific emphasis on heterochromatic regions of the genome.
Taddei
Angela
A
Institut Curie, Research Section, UMR 218 du CNRS, 26 Rue d'Ulm, 75248 Paris cedex 05, France.
Roche
Danièle
D
Bickmore
Wendy A
WA
Almouzni
Geneviève
G
D002453:Cell Cycle / Q000187:drug effects*; D006570:Heterochromatin / Q000187:drug effects / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000187:drug effects / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy*
D006570:Heterochromatin; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C012589:trichostatin A