NoRC negatively regulates rRNA expression

Stable Identifier
R-HSA-427413
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Pathway
Species
Homo sapiens
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Methylation of histones and DNA negatively regulates rRNA expression
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The Nucleolar Remodeling Complex (NoRC) comprising TIP5 (BAZ2A) and the chromatin remodeller SNF2H (SMARCA5) silences rRNA gene (reviewed in Santoro and Grummt 2001, Grummt 2007, Preuss and Pikaard 2007, Birch and Zommerdijk 2008, McStay and Grummt 2008, Grummt and Langst 2013). The TAM domain of TIP5 (BAZ2A) binds promoter-associated RNA (pRNA) transcribed from the intergenic spacer region of rDNA. The pRNA bound by TIP5 is required to direct the complex to the main promoter of the rRNA gene possibly by triple helix formation between pRNA and the rDNA. The PHD domain of TIP5 binds histone H4 acetylated at lysine-16. Transcription Termination Factor-I (TTF-I) binds to a promoter-proximal terminator (T0 site) in the rDNA and interacts with the TIP5 subunit of NoRC. NoRC also interacts with the SIN3-HDAC complex, HDAC1, HDAC2, DNMT1, and DNMT3B. DNMT3B interacts with a triple helix formed by pRNA and the rDNA. HDAC1, DNMT1, and DNMT3B have been shown to be required for proper DNA methylation of silenced rRNA gene copies, although the catalytic activity of DNMT3B was not required.

Literature References
PubMed ID Title Journal Year
17439825 rRNA gene silencing and nucleolar dominance: insights into a chromosome-scale epigenetic on/off switch

Preuss, S, Pikaard, CS

Biochim Biophys Acta 2007
17613545 Different epigenetic layers engage in complex crosstalk to define the epigenetic state of mammalian rRNA genes

Grummt, I

Hum Mol Genet 2007
11583633 Molecular mechanisms mediating methylation-dependent silencing of ribosomal gene transcription

Santoro, R, Grummt, I

Mol Cell 2001
18616426 The epigenetics of rRNA genes: from molecular to chromosome biology

McStay, B, Grummt, I

Annu Rev Cell Dev Biol 2008
23063748 Epigenetic control of RNA polymerase I transcription in mammalian cells

Grummt, I, Längst, G

Biochim. Biophys. Acta 2013
18631128 Structure and function of ribosomal RNA gene chromatin

Birch, JL, Zomerdijk, JC

Biochem Soc Trans 2008
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