It Takes a Village of Chromatin Remodelers to Regulate rDNA Expression.

Abstract

Ribosome biogenesis is one of the most fundamental and energetically demanding cellular processes. In humans, the ribosomal DNA (rDNA) repeats span a large region of DNA and comprise 200 to 600 copies of a ~43 kb unit spread over five different chromosomes. Control over ribosome biogenesis is closely tied to the regulation of the chromatin environment of this large genomic region. The proportion of rDNA loci which are active or silent is altered depending on the proliferative or metabolic state of the cell. Repeat silencing is driven by epigenetic changes culminating in a repressive heterochromatin environment. One group of proteins facilitating these epigenetic changes in response to growth or metabolic demands are ATP-dependent chromatin remodeling protein complexes that use ATP hydrolysis to reposition nucleosomes. Indeed, some chromatin remodelers are known to have indispensable roles in regulating the chromatin environment of rDNA. In this review, we highlight these proteins and their complexes and describe their mechanistic roles at rDNA. We also introduce the developmental disorders arising from the dysfunction of these proteins and discuss how the consequent dysregulation of rDNA loci may be reflected in the phenotypes observed.