Positive epigenetic regulation of rRNA expression

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R-HSA-5250913
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Pathway
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Homo sapiens
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Transcription of rRNA genes is controlled by epigenetic activation and repression according to the metabolic requirements of the cell (reviewed in Percipalle and Farrants 2006, McStay and Grummt 2008, Goodfellow and Zomerdijk 2012, Grummt and Langst 2013). Depending on the growth state of the cell, about half of the approximately 400 rRNA genes are expressed and these have the modifications characteristic of active chromatin: unmethylated DNA and acetylated histones. Repressed genes generally have methylated DNA and histone H3 methylated at lysine-9. Regulators of activation include ERCC6 (CSB), histone acetylases such as KAT2B (PCAF), and the B-WICH complex. Dysregulation of RNA polymerase I transcription plays a role in disease (reviewed in Hannan et al. 2013).
The B-WICH complex positively regulates rRNA expression by remodeling chromatin and recruiting histone acetyltransferases that modify histones to transcriptionally active states
ERCC6 (CSB) and EHMT2(G9a) positively regulate rRNA expression by ERCC6 recruiting the histone methyltransferase EHMT2 (also known as G9a) which dimethylates histone H3 at lysine-9 within the transcribed regions of rRNA genes.
ERCC6 (CSB) and KAT2B (PCAF) positively regulate rRNA expression by ERCC6 recruiting the histone acetyltransferase KAT2B to the promoter where KAT2B acetylates histone H4 at several lysine residues and histone H3 at lysine-9. The acetylated chromatin facilitates the assembly of RNA polymerase I initiation complex.

Literature References
PubMed ID Title Journal Year
16574391 Chromatin remodelling and transcription: be-WICHed by nuclear myosin 1

Percipalle, P, Farrants, AK

Curr. Opin. Cell Biol. 2006
23150253 Basic mechanisms in RNA polymerase I transcription of the ribosomal RNA genes

Goodfellow, SJ, Zomerdijk, JC

Subcell. Biochem. 2012
23153826 Dysregulation of RNA polymerase I transcription during disease

Hannan, KM, Sanij, E, Rothblum, LI, Hannan, RD, Pearson, RB

Biochim. Biophys. Acta 2013
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
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