The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expression
- 1 October 2008
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 22 (19), 2664-2676
- https://doi.org/10.1101/gad.1703008
Abstract
Histone monoubiquitylation is implicated in critical regulatory processes. We explored the roles of histone H2B ubiquitylation in human cells by reducing the expression of hBRE1/RNF20, the major H2B-specific E3 ubiquitin ligase. While H2B ubiquitylation is broadly associated with transcribed genes, only a subset of genes was transcriptionally affected by RNF20 depletion and abrogation of H2B ubiquitylation. Gene expression dependent on RNF20 includes histones H2A and H2B and the p53 tumor suppressor. In contrast, RNF20 suppresses the expression of several proto-oncogenes, which reside preferentially in closed chromatin and are modestly transcribed despite bearing marks usually associated with high transcription rates. Remarkably, RNF20 depletion augmented the transcriptional effects of epidermal growth factor (EGF), increased cell migration, and elicited transformation and tumorigenesis. Furthermore, frequent RNF20 promoter hypermethylation was observed in tumors. RNF20 may thus be a putative tumor suppressor, acting through selective regulation of a distinct subset of genes.Keywords
This publication has 58 references indexed in Scilit:
- A positive feedback loop between the p53 and Lats2 tumor suppressors prevents tetraploidizationGenes & Development, 2006
- Transcriptional regulation by histone ubiquitination and deubiquitinationGenes & Development, 2003
- Prolonged culture of telomerase-immortalized human fibroblasts leads to a premalignant phenotype.2003
- Transcriptional activation via sequential histone H2B ubiquitylation and deubiquitylation, mediated by SAGA-associated Ubp8Genes & Development, 2003
- A Conserved RING Finger Protein Required for Histone H2B Monoubiquitination and Cell Size ControlMolecular Cell, 2003
- Genome-wide histone modifications: gaining specificity by preventing promiscuityCurrent Opinion in Cell Biology, 2002
- Methylation of Histone H3 by COMPASS Requires Ubiquitination of Histone H2B by Rad6Published by Elsevier BV ,2002
- Trans-histone regulatory pathway in chromatinNature, 2002
- Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeastNature, 2002
- Translating the Histone CodeScience, 2001