SIR2,Molecular Analysis of Aging : NAD Dependent Histone Deacetylase, SIR2

SIR2 and its homologues are newly identified nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases. Yeast (Saccharomyces cerevisiae) SIR2 silences transcription at silent mating loci, teromeres and ribosomal DNA (rDNA), and that also suppresses recombination in rDNA. Yeast and mammalian SIR2 homologue (SIR2 alpha) was found to specifically deacetylate acetylated lysine residues of histone H3 and H4 in a NAD-dependent manner. The deacetylation of histones has been identified as important for silencing. Interestingly, increase in dosages of SIR2 gene extended the life span in yeast and Caenorhabditis elegans. Although recent studies showed that Sir2 alpha directly binds and deacetylates p53 to repress p53-dependent apoptosis, the distribution and physiological functions of SIR2 family in mammals still remain to be elucidated. We found that SIR2 alpha and SIR3, both of which are mammalian SIR2 homologues, are expressed in neural stem cells. The expression of these SIRs promptly disappeared after differentiation. We assume that these SIRs may play a significant role in the proliferation and/or differentiation of neural stem cells