Abstract
BackgroundHistone deacetylases (HDACs) are the proteins responsible for removing the acetyl group from lysine residues of core histones in chromosomes, a crucial component of gene regulation. Eleven known HDACs exist in humans and most other vertebrates. While the basic function of HDACs has been well characterized and new discoveries are still being made, the transcriptional regulation of their corresponding genes is still poorly understood.ResultsHere, we conducted a computational analysis of the eleven HDAC promoter sequences in 25 vertebrate species to determine whether transcription factor binding sites (TFBSs) are conserved in HDAC evolution, and if so, whether they provide useful information about HDAC expression and function. Furthermore, we used tissue-specific information of transcription factors to investigate the potential expression patterns of HDACs in different human tissues based on their transcription factor binding sites. We found that the TFBS profiles of most of the HDACs were well conserved in closely related species for all HDAC promoters except HDAC7 and HDAC10. HDAC5 had particularly strong conservation across over half of the species studied, with nearly identical profiles in the primate species. Our comparisons of TFBSs with the tissue specific gene expression profiles of their corresponding TFs showed that most HDACs had the ability to be ubiquitously expressed. A few HDAC promoters exhibited the potential for preferential expression in certain tissues, most notably HDAC11 in gall bladder, while HDAC9 seemed to have less propensity for expression in the nervous system.ConclusionsIn general, we found evolutionary conservation in HDAC promoters that seems to be more prominent for the ubiquitously expressed HDACs. In turn, when conservation did not follow usual phylogeny, human TFBS patterns indicated possible functional relevance. While we found that HDACs appear to uniformly expressed, we confirm that the functional differences in HDACs may be less a matter of location of activity than a question of which proteins and which acetyl groups they may be acting on.
Highlights
Histone deacetylases (HDACs) are the proteins responsible for removing the acetyl group from lysine residues of core histones in chromosomes, a crucial component of gene regulation
Evolutionary conservation of Transcription factor binding site (TFBS) in HDAC promoters We found that human TFBS patterns in HDAC promoters are evolutionarily conserved across all HDACs, with only HDACs 5, 7 and 10 indicating unusual patterns of TFBS distribution along the promoter region
TFBSs have a high evolutionary turnover rate such that even closely related species may not have conserved binding sites on their promoters [54]. This may explain some of the differences we observed in TFBS pattern along the promoters of HDACs from different species
Summary
Histone deacetylases (HDACs) are the proteins responsible for removing the acetyl group from lysine residues of core histones in chromosomes, a crucial component of gene regulation. Histone deacetylases (HDACs) remove the acetyl group from lysine residues of the N-terminal tail of core histones, allowing the repression of transcription. These metal binding proteins are mostly active in large multiprotein complexes, and can act on non-histone proteins. The HDAC proteins have been well characterized, and the position of their active site(s), their genomic position and cellular localization are well established (Table 1) Their modes of action have been investigated extensively over the last two decades, with particular emphasis on HDAC inhibitors as possible drugs for use in cancer therapy [4, 5].
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