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

Efrat Shema, Itay Tirosh, Yael Aylon, Jing Huang, Chaoyang Ye, Neta Moskovits, Nina Raver-Shapira, Neri Minsky, Judith Pirngruber, Gabi Tarcic, Pavla Hublarova, Lilach Moyal, Mali Gana-Weisz, Yosef Shiloh, Yossef Y-arden, Steven A. Johnsen, Borivoj Vojtesek, Shelley L. Berger, Moshe Oren

Research output: Contribution to journalArticle

179 Scopus citations

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 hBREl/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.

Original languageEnglish (US)
Pages (from-to)2664-2676
Number of pages13
JournalGenes and Development
Volume22
Issue number19
DOIs
StatePublished - Oct 1 2008

Keywords

  • Bre1
  • H2B ubiquitylation
  • RNF20
  • Transcription
  • Tumor suppressor

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Fingerprint Dive into the research topics of 'The histone H2B-specific ubiquitin ligase RNF20/hBREl acts as a putative tumor suppressor through selective regulation of gene expression'. Together they form a unique fingerprint.

  • Cite this

    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., Y-arden, Y., Johnsen, S. A., Vojtesek, B., Berger, S. L., & Oren, M. (2008). The histone H2B-specific ubiquitin ligase RNF20/hBREl acts as a putative tumor suppressor through selective regulation of gene expression. Genes and Development, 22(19), 2664-2676. https://doi.org/10.1101/gad.1703008