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PMID: 18832071 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expression.

Genes & development ·Vol. 22 ·No. 19 ·2008-10-01 ·Pages 2664-76

Shema E, Tirosh I, Aylon Y, Huang J, Ye C, Moskovits N, Raver-Shapira N, Minsky N, Pirngruber J, Tarcic G, Hublarova P, Moyal L, Gana-Weisz M, Shiloh Y, Yarden Y, Johnsen SA, Vojtesek B, Berger SL, Oren M

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.

MeSH Terms
Animals Breast Neoplasms/genetics,metabolism Cell Movement Cell Transformation, Neoplastic Chromatin/genetics,metabolism DNA Methylation DNA, Neoplasm/chemistry,genetics,metabolism Epidermal Growth Factor/pharmacology Female Gene Expression Regulation/drug effects HeLa Cells Histones/chemistry,metabolism Humans Mice Mice, Nude Promoter Regions, Genetic RNA Polymerase II/metabolism RNA, Small Interfering/genetics Suppression, Genetic Tumor Suppressor Protein p53/genetics,metabolism Tumor Suppressor Proteins/genetics,metabolism Ubiquitin-Protein Ligases/antagonists & inhibitors,genetics,metabolism Ubiquitination
Chemicals
Chromatin DNA, Neoplasm Histones RNA, Small Interfering TP53 protein, human Tumor Suppressor Protein p53 Tumor Suppressor Proteins Epidermal Growth Factor RNF20 protein, human RNF20 protein, mouse Ubiquitin-Protein Ligases RNA Polymerase II
Authors & Affiliations
19 authors, click to expand affiliations / ORCID
Shema Efrat
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Tirosh Itay
Aylon Yael
Huang Jing
Ye Chaoyang
Moskovits Neta
Raver-Shapira Nina
Minsky Neri
Pirngruber Judith
Tarcic Gabi
Hublarova Pavla
Moyal Lilach
Gana-Weisz Mali
Shiloh Yosef
Yarden Yossef
Johnsen Steven A
Vojtesek Borivoj
Berger Shelley L
Oren Moshe
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1703008
Published
2008-10-01
Pages
2664-76
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC2559905
Subset
IM
Grants
NCI NIH HHS · R01 CA078831 · United States
NCI NIH HHS · R37 CA040099 · United States
NCI NIH HHS · R37 CA40099 · United States
Corrections
CommentIn
PMID: 18923072
ErratumIn
PMID: 29051390
External Links
PubMed source DOI: 10.1101/gad.1703008 PMC Full Text View journal details
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