Transcriptional regulation of neuronal genes and its effect on neural functions: NAD-dependent histone deacetylase SIRT1 (Sir2alpha).

Sir2 (silent information regulator 2) is an NAD-dependent deacetylase that is broadly conserved from bacteria to humans. It catalyzes a unique deacetylation reaction using NAD, and specific inhibitors and activators of its activity have been discovered. In yeast, Sir2 deacetylates histones and participates in transcription silencing and the suppression of recombination. Sir2 is also implicated in the regulation of aging, because its increased expression extends the lifespan of yeast and nematodes. Mammalian SIRT1 (Sir2alpha) is a member of the Sir2 family. Recently, SIRT1 was shown to interact with various transcription factors such as p53, forkhead transcription factor (FOXO) family proteins, and MyoD, and to participate in stress tolerance, differentiation, and development.