Abstract
BackgroundHistone deacetylases are enzymes that modify core histones and play key roles in transcriptional regulation, chromatin assembly, DNA repair, and recombination in eukaryotes. Three types of related histone deacetylases (classes 1, 2, and 4) are widely found in eukaryotes, and structurally related proteins have also been found in some prokaryotes. Here we focus on the evolutionary history of the class 4 histone deacetylase family.ResultsThrough sequence similarity searches against sequenced genomes and expressed sequence tag data, we identified members of the class 4 histone deacetylase family in 45 eukaryotic and 37 eubacterial species representative of very distant evolutionary lineages. Multiple phylogenetic analyses indicate that the phylogeny of these proteins is, in many respects, at odds with the phylogeny of the species in which they are found. In addition, the eukaryotic members of the class 4 histone deacetylase family clearly display an anomalous phyletic distribution.ConclusionThe unexpected phylogenetic relationships within the class 4 histone deacetylase family and the anomalous phyletic distribution of these proteins within eukaryotes might be explained by two mechanisms: ancient gene duplication followed by differential gene losses and/or horizontal gene transfer. We discuss both possibilities in this report, and suggest that the evolutionary history of the class 4 histone deacetylase family may have been shaped by horizontal gene transfers.
Highlights
Histone deacetylases are enzymes that modify core histones and play key roles in transcriptional regulation, chromatin assembly, DNA repair, and recombination in eukaryotes
Derivation of a comprehensive set of class 4 histone deacetylases (HDACs) In a survey of animal HDACs, we found by Blast BLAST searches against the National Center for Biotechnology Information (NCBI) NR database that some animal class 4 HDACs are more similar to eubacterial HDACs than to those of other eukaryotes
In order to conduct a phylogenetic analysis of these sequences on the largest possible sampling of HDACs, we retrieved a large number of protein sequences of class 4 HDACs (HDAC11-related) by means of BLAST searches against the NCBI NR database, and against various finished and unfinished genomes and expressed sequence tag (EST) data
Summary
Histone deacetylases are enzymes that modify core histones and play key roles in transcriptional regulation, chromatin assembly, DNA repair, and recombination in eukaryotes. Three types of related histone deacetylases (classes 1, 2, and 4) are widely found in eukaryotes, and structurally related proteins have been found in some prokaryotes. The packaging of DNA restricts its accessibility to proteins such as transcription factors, and the transcriptional activation of many genes requires chromatin modifications such as reversible acetylation of the core histones [2]. The steadystate level of acetylation is controlled by the antagonistic activities of two types of enzymes: histone acetyltransferases and histone deacetylases (HDACs). HDACs have recently attracted considerable attention because chemical inhibitors of HDACs induce growth arrest, differentiation, and/ or apoptosis of cancer cells both in vitro and in vivo, and may represent a new class of anti-tumor agents [4]
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