Reactome: A Curated Pathway Database

NoRC negatively regulates rRNA expression

Stable Identifier
R-HSA-427413
Type
Pathway
Species
Homo sapiens
Compartment
Synonyms
Methylation of histones and DNA negatively regulates rRNA expression
Locations in the PathwayBrowser
Summation

Only about half of the rRNA gene copies in a cell are expressed. The remaining copies are silenced by modifications to histones and DNA (reviewed in Santoro and Grummt 2001, Grummt 2007, Preuss and Pikaard 2007, Birch and Zomerdijk 2008, McStay and Grummt 2008, Grummt and Langst 2013). The promoters of silenced rRNA gene copies have methylated cytosine and histone H3 dimethylated at lysine-9. As inferred from mouse, silencing is initiated by recruitment of the Nucleolar Remodeling Complex (NoRC) to the promoter through interaction with TTF-I and intergenic spacer transcripts. NoRC shifts a nucleosome near the start of rRNA transcription into a more repressive location and recruits Histone Deacetylase 1 and 2 (HDAC1, HDAC2) and DNA Methyltransferase 1 and 3b (DNMT1, DNMT3b). Interaction with a Histone Methyltransferase is also assumed. Deacetylation of histones is required for DNA methylation but not for methylation of histone H3. Methylcytosine at the rRNA promoter binds Methyl Domain Binding protein 2 (MBD2) which inhibits expression of the rRNA gene.

Literature References
Participants
Participant Of
Inferred From
Orthologous Events