Intergenic transcripts originating from a subclass of ribosomal DNA repeats silence ribosomal RNA genes in trans

• Published in: EMBO reports Vol. 11; no. 1; pp. 52 - 58
• Main Authors: Santoro, Raffaella, Schmitz, Kerstin-Maike, Sandoval, Juan, Grummt, Ingrid
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.01.2010; Blackwell Publishing Ltd; Nature Publishing Group
• Subjects: Animals; Chromatin Assembly and Disassembly - genetics; Chromatin Assembly and Disassembly - physiology; Chromatin remodeling; DNA methylation; DNA Methylation - genetics; DNA Methylation - physiology; DNA, Intergenic - genetics; DNA, Ribosomal - genetics; DNA-directed RNA polymerase; DNA-Directed RNA Polymerases - genetics; DNA-Directed RNA Polymerases - metabolism; Epigenesis, Genetic - genetics; epigenetic silencing; epigenetics; Gene Silencing; Genes; Mice; Molecular biology; NIH 3T3 Cells; non-coding RNA; NoRC; Nucleoli; Nucleotides; Promoter Regions, Genetic; Promoters; rDNA; Repeated DNA sequences; Repetitive Sequences, Nucleic Acid - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA polymerase; RNA, Ribosomal - genetics; RNA, Untranslated - genetics; RNA, Untranslated - metabolism; rRNA; S Phase; Scientific Report; Spacer; spacer promoter; Transcription, Genetic
• ISSN: 1469-221X; 1469-3178
• DOI: 10.1038/embor.2009.254

Epigenetic silencing of a fraction of ribosomal DNA (rDNA) requires association of the nucleolar chromatin‐remodelling complex NoRC to 150–250 nucleotide RNAs (pRNA) that originate from an RNA polymerase I promoter located in the intergenic spacer separating rDNA repeats. Here, we show that NoRC‐associated pRNA is transcribed from a sub‐fraction of hypomethylated rRNA genes during mid S phase, acting in trans to inherit DNA methylation and transcriptional repression of late‐replicating silent rDNA copies. The results reveal variability between individual rDNA clusters with distinct functional consequences. The Grummt lab studies epigenetic silencing of rRNA genes by the NoRC/pRNA complex and shows that NoRC‐associated pRNA is transcribed from a subfraction of hypomethylated rRNA genes during mid S‐phase, acting in trans to inherit DNA methylation and transcriptional repression of late replicating silent rDNA copies. These results reveal variability between individual rDNA clusters with distinct functional consequences.