Sirtuins and Histone deactylases (HDACs)
Eukaryotic DNA is packed in a high level structure called chromatin, resulting from the assembly of an elementary unit, the nucleosome, and an octameric structure obtained from eight proteins called histones [1]. Histone deacetylation is a reversible process whereby histone and non-histone protein transfer the acetyl moiety from acetyl co-enzyme A (CoA) to lysines while histone acetylation is the direct opposite process whereby acetyl groups are removed from lysines. These two processes play an extremely important role in the transcription regulation of cells. This is due to the fact that DNA is wrapped around histones, and, by transferring or removing an acetyl group to histones, genes can be turned on and off [2,3].
Histone acetyl-transferases (HATs) add acetyl groups to lysine while histone deacetylases (HDACs) remove the acetyl groups. In general, HATs act as transcriptional activators. Acetylation of lysine neutralizes the positive charge normally present and subsequently promotes a more relaxed chromatin structure by reducing affinity between histone and the negatively charged …show more content…
Sirtuins first gained prominence when it was reported that their activation might be related to longevity [16,17]. However, there have since been conflicting views on that matter and the attention has been shifted to sirtuin inhibitors as they have been linked to the pathogenesis of cancer [18] and neurological diseases [19,20]. SIRT1 is the direct homologue of the yeast Sir2 and has a wide range of cellular functions such as modulating cell survival and regulating the transcriptional activities of NF-ĸB [21], p53 [22] and FOXO proteins [23]. While SIRT1 is located in the nucleus, SIRT2 is a predominantly cytoplasmic protein and is able to deacetylate H4K16 and several cytoplasmic substrates, including α-tubulin
Eukaryotic DNA is packed in a high level structure called chromatin, resulting from the assembly of an elementary unit, the nucleosome, and an octameric structure obtained from eight proteins called histones [1]. Histone deacetylation is a reversible process whereby histone and non-histone protein transfer the acetyl moiety from acetyl co-enzyme A (CoA) to lysines while histone acetylation is the direct opposite process whereby acetyl groups are removed from lysines. These two processes play an extremely important role in the transcription regulation of cells. This is due to the fact that DNA is wrapped around histones, and, by transferring or removing an acetyl group to histones, genes can be turned on and off [2,3].
Histone acetyl-transferases (HATs) add acetyl groups to lysine while histone deacetylases (HDACs) remove the acetyl groups. In general, HATs act as transcriptional activators. Acetylation of lysine neutralizes the positive charge normally present and subsequently promotes a more relaxed chromatin structure by reducing affinity between histone and the negatively charged …show more content…
Sirtuins first gained prominence when it was reported that their activation might be related to longevity [16,17]. However, there have since been conflicting views on that matter and the attention has been shifted to sirtuin inhibitors as they have been linked to the pathogenesis of cancer [18] and neurological diseases [19,20]. SIRT1 is the direct homologue of the yeast Sir2 and has a wide range of cellular functions such as modulating cell survival and regulating the transcriptional activities of NF-ĸB [21], p53 [22] and FOXO proteins [23]. While SIRT1 is located in the nucleus, SIRT2 is a predominantly cytoplasmic protein and is able to deacetylate H4K16 and several cytoplasmic substrates, including α-tubulin