Sirtuins in Epigenetic Regulation

Sirtuins are considered as important players in epigenetics and therefore, much research is being done on it. SIR2-mediated silencing is achieved by recruitment of SIR2 to different chromatin locations. SIR2 recruitment to the silent mating loci and telomeres requires RAP1 (repressor activator protein 1), which binds to specific silencer DNA sequences. SIR2, as a member of the RENT complex, was also found to be important to prevent recombination events at the rDNA loci. The SIR proteins are also required for repair of double-strand DNA breaks. SIR2-dependent gene silencing is regulated by the protein Arg methyltransferase HMT1 (HnRNP methyltransferase 1) in yeast. Lack of HMT1 activity leads to decreased histone H4R3 methylation, increased histone acetylation, and increased transcription from silent chromatin regions and increased mitotic rDNA recombination. The most important mechanism by which SIRT1 promotes cellular response to stress is the transcription silencing associated with FH formation.