Chromatin Turn Ons and Turn Offs of Ribosomal RNA Genes

Abstract

Eukaryotes have hundreds (sometimes thousands) of ribosomal RNA (rRNA) genes whose transcription by RNA polymerase I helps establish the proliferative ability of cells by dictating the pace of ribosome production and protein synthesis. Interestingly, only a subset of the total rRNA gene pool is active at any one time, making rRNA genes attractive for understanding the dynamic balance between gene silencing and activation. However, the fact that rRNA genes are essentially identical in sequence in a pure species has been an obstacle to telling apart the active and inactive genes. Nature has provided one solution to this conundrum in the form of the epigenetic phenomenon, nucleolar dominance: the transcriptional silencing of one parental set of rRNA genes in a genetic hybrid. Parental genes in hybrids typically differ in sequence as well as expression, allowing a definition of the chromatin modifications of rRNA genes in the on and off states in vivo. By exploiting nucleolar dominance in plants, we recently showed that concerted changes in DNA methylation and histone methylation comprise an epigenetic switch that turns rRNA genes on and off. Independent studies using mouse and human cells have led to similar conclusions, implicating chromatin modifications as important components of the regulatory networks that control the effective dosage of active rRNA genes.