Lysine acetylation

One of the most-studied covalent modifications is the acetylation of the lysine residues of histone tails. The acetylation state of lysines of nucleosomal histones modulates chromatin structure and regulates gene transcriptional activity. The balance of lysine acetylation is controlled by the antagonistic action of two enzyme families histone deacetylases (HDACs) and histone acetyltransferases (HATs). In humans there are essentially three main HDAC subclasses [6]. 

Experimental results regarding the role of the histone tails indicate that these histone domains play a critical role in chromatin folding [358,365]. Removal as well as the modification (acetylation) of the lysine amino acids within these regions produces an imbalance of the electrostatic interactions, which results in a hierarchically impaired folding ability (H3/H4-H2A/H2B>H3/H4>H2A/H2B) of the chromatin fiber [358,366-369]. Therefore, sources of histone tail variability (histone variants and post-translational modifications other than lysine acetylation) are also likely to alter the extent of folding of chromatin. 

Yang, X.J. and Seto, E. (2008) Lysine acetylation codified crosstalk with other posttranslational modifications. 

The equilibrium of reversible histone lysine acetylation is maintained by histone deacetylases (H D ACs) on one hand and histone acetyltransferases on the other hand. Human histone deacetylases can be separated into four classes [15]. HDACs of class I, II and IV are zinc-dependent amidohydrolases, whereas class III HDACs, also referred to as sirtuins, have a mechanism that is dependent on NAD [16]. As histone deacetylases have been widely studied, it is not surprising that there are also a large number of assays existing that have helped to characterize modulators of these enzymes and subsequently the enzymes themselves. 

Schwer, B., Bunkenborg, J., Verdin, R.O., Andersen, J.S. and Verdin, F. (2006) Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. Proceedings... 

In cells of the mammary gland, either in normal epithelial or in cancerous cells, the packaging of chromosomal DNA into chromatin restricts the access of the transcription machinery, thereby causing transcriptional repression. The basic N-termini of histones are subject to post-translational modifications, including lysine acetylation, lysine and arginine methylation, serine phosphorylation and ubiquitinylation [56]. It has been proposed in the histone code hypothesis that the intricate pattern of modifications of the N-terminal histone tail influences gene regulation [57]. 

Bacillus subtilis Soil microbe Label-free Protein-lysine acetylation (168)... 

Xiang-Jiao Y. Lysine acetylation and the bromodomain a new partnership for signaling. Bioessays 2004 26 1076-1087. 

Other natural sources of salicylates are listed in Table 1. There are separate monographs on acetylsali-cylic acid (aspirin), benorilate, diflunisal, lysine acetyl-salicylate, and salsalate. Methyl salicylate is covered under Gaultheria procumbens in the monograph on the Ericaceae. 

Naguib M, Farag H, Magbagbeola JA. Effect of pre-treatment with lysine acetyl salicylate on suxametho-nium-induced myalgia. Br J Anaesth 1987 59(5) 606-10. 

The analgesic efficacy of tramadol can be further enhanced by adding injectable lysine acetyl salicylate (aspirin) after orthopedic surgery with no significant increase in adverse effects (26). 

Pang W, Huang S, Tung CC, Huang MH. Patient-controlled analgesia with tramadol versus tramadol plus lysine acetyl salicylate. Anesth Analg 2000 91(5) 1226-9. 

It is now clear that lysine acetylation by HATs and deacetylation by HDACs can also occur in non-histone proteins, implicating their involvement in a variety of cellular processes aside from transcription [208]. The regulation of protein stability is an important example (reviewed in [209]). 

Choudhary C et al (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325(5942) 834-840... 

Caron C, Boyault C, Khochbin S (2005) Regulatory cross-talk between lysine acetylation and ubiquitination role in the control of protein stability. Bioessays 27(4) 408-415... 

In general, transcriptional activators can bind and recruit HATs while transcriptional repressors and corepressors interact with HDACs. The unwinding of DNA offhistones by lysine acetylation is conceptually helpful for understanding the action of HATs and HDACs. It is, nevertheless, a simplistic and incomplete explanation for the way in which these enzymes control gene expression. For example, in some cases [4] inhibition of HDACs can lead to a counterintuitive decrease in gene expression. It is likely that the overall pattern of histone modification (of which acetylation is but one example) represents... 

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