%0 Journal Article
%T Differential effects of class I isoform histone deacetylase depletion and enzymatic inhibition by belinostat or valproic acid in HeLa cells
%A Marielle Dejligbjerg
%A Morten Grauslund
%A Thomas Litman
%A Laura Collins
%A Xiaozhong Qian
%A Michael Jeffers
%A Henri Lichenstein
%A Peter Jensen
%A Maxwell Sehested
%J Molecular Cancer
%D 2008
%I BioMed Central
%R 10.1186/1476-4598-7-70
%X HDAC KD showed anti-proliferative effects, although to a lesser extent than HDACi treatment. Moreover, we found a 2-fold increased resistance of HDAC1 knockdown cells to belinostat, suggesting this isoenzyme as a selective target. While both HDACi treatment and individual class I HDAC KD produce significant transcriptional effects, three-times higher for HDACi, the gene-expression profiles of class I HDAC KD compared with that obtained by HDACi treatment exhibited less than 4% of altered genes in common between the two modes of inhibition. Further, cell-specific effects of HDAC KD are evident by comparison with a recent study in a different cell line.The increased resistance to belinostat in response to HDAC1 depletion indicates the possibility of using this isoform as a predictive biomarker of response to HDACi treatment. Further, the transcriptional response to chemical inhibition of HDACs is very different from that of KD of individual class I HDAC isoforms. These data suggest that the anti-tumor effect of HDACi is indeed linked to class I inhibition, but may be more complex than simply targeting individual HDAC enzymes.The transcription of genes is highly regulated by epigenetic chromatin modifications, including the acetylation of lysine residues protruding from nucleosomal histones. Thus, histone acetylation status is maintained by the opposing actions of histone acetyl transferase and histone deacetylase (HDAC) enzymes [1,2]. HDACs modify gene expression via multiple mechanisms. The deacetylation of histones causes general chromosome condensation, and also plays a role in transcriptional regulation by forming a combinatorial 'histone code' that regulates downstream responses [2,3]. Additionally, a variety of non-histone targets such as transcription factors, structural and chaperone proteins are targeted by HDAC enzymes [4]. The Zn2+-dependent mammalian HDAC isoenzymes are divided into three classes based on their homology to yeast deacetylase proteins. Class
%U http://www.molecular-cancer.com/content/7/1/70