Epigenetic silencing of RNA polymerase I transcription

Ribosomal RNA genes can be silenced on a large scale, by the inactivation of entire nucleolus organizer regions (NORs) in genetic hybrids, or on a smaller scale, by silencing individual rRNA genes within an NOR.Techniques that probe the accessibility of rRNA genes in a chromatin environment, including those using the sensitivity to deoxyribonucleases or the DNA crosslinking agent psoralen, have shown that changes in chromatin accessibility correlate with changes in rRNA gene transcription in yeast, plants and mammals.Silenced rRNA genes are derepressed if DNA methylation or histone deacetylation is perturbed, implicating chromatin modifications in rRNA gene silencing.New insight into rRNA gene silencing mechanisms has come from the characterization of NoRC, a SNF2h-containing chromatin remodelling complex that is recruited to mammalian rRNA gene promoters by the DNA-binding factor TTF-I. NoRC interaction with the rRNA gene promoter brings about transcriptional silencing coincident with de novo cytosine methylation, histone deacetylation and histone H3 lysine 9 methylation.Future challenges include the need to understand how rRNA genes are chosen for activation or repression, how NoRC is targeted to establish or maintain silencing, how overall chromatin organization is affected by localized rRNA gene silencing and how epigenetic marks are inherited.