A metabolic throttle regulates the epigenetic state of rDNA

The synthesis of ribosomal RNA ( rRNA) is carefully tuned to match nutritional conditions. In this issue, Murayama et al. ( 2008) describe a mechanism that couples the energy status of the cell to heterochromatin formation and silencing of rRNA genes. They show that an altered NAD+/ NADH ratio in response to glucose starvation regulates the silencing activity of eNoSC, a complex consisting of the NAD(+)- dependent histone deacetylase SIRT1, the histone methyltransferase SUV39H1, and a new protein called nucleomethylin (NML). These results suggest a mechanism that links cell physiology to rDNA silencing, which in turn is a prerequisite for nucleolar integrity and cell survival.