The nucleolar remodeling complex NoRC mediates heterochromatin formation and silencing of ribosomal gene transcription

Abstract

Epigenetic control mechanisms silence about half of the ribosomal RNA (rRNA) genes in metabolically active cells. In exploring the mechanism by which the active or silent state of rRNA genes is inherited, we found that NoRC, a nucleolar remodeling complex containing Snf2h (also called Smarca5, SWI/SNF-related matrix-associated actin-dependent regulator of chromatin, subfamily a, member 5), represses rDNA transcription. NoRC mediates rDNA silencing by recruiting DNA methyltransferase and histone deacetylase activity to the rDNA promoter, thus establishing structural characteristics of heterochromatin such as DNA methylation, histone hypoacetylation and methylation of the Lys9 residue of histone H3. These results indicate that active and inactive rRNA genes can be demarcated by their associated proteins, and link chromatin remodeling to DNA methylation and specific histone modifications.