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The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expression — Genes & Developmentby: 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 Yarden, Steven A. Johnsen, Borivoj Vojtesek, Shelley L. Berger, Moshe Oren, J. Pirngruber, G. Tarcic, P. Hublarova, L. Moyal, M. Gana-Weisz, Y. Shiloh, Y. Yarden, S. A. Johnsen, B. Vojtesek, S. L. Berger, M. Oren
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Notes for this articleThis is the paper described in the Espinosa commentary about role of human Bre1 as a tumor suppressor. No time to read the actual article now, but Espinosa review is great.
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AbstractHistone 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 promoter hypermethylation was observed in tumors. RNF20 may thus be a putative tumor suppressor, acting through selective regulation of a distinct subset of genes.
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