Browsing by Author "Minsky, Neri"

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    CDK9 directs H2B monoubiquitination and controls replication-dependent histone mRNA 3 '-end processing
    (Nature Publishing Group, 2009)
    Pirngruber, Judith
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    Shchebet, Andrei
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    Schreiber, Lisa
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    Shema, Efrat
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    Minsky, Neri
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    Chapman, Rob D.
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    Eick, Dirk
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    Aylon, Yael
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    Oren, Moshe
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    Johnsen, Steven A.  
    Post-translational histone modifications have essential roles in controlling nuclear processes; however, the specific mechanisms regulating these modifications and their combinatorial activities remain elusive. Cyclin-dependent kinase 9 (CDK9) regulates gene expression by phosphorylating transcriptional regulatory proteins, including the RNA polymerase II carboxy-terminal domain. Here, we show that CDK9 activity is essential for maintaining global and gene-associated levels of histone H2B monoubiquitination (H2Bub1). Furthermore, CDK9 activity and H2Bub1 help to maintain correct replication-dependent histone messenger RNA (mRNA) 3'-end processing. CDK9 knockdown consistently resulted in inefficient recognition of the correct mRNA 3'-end cleavage site and led to increased read-through of RNA polymerase II to an alternative downstream polyadenylation signal. Thus, CDK9 acts to integrate phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing.
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    The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expression
    (Cold Spring Harbor Lab Press, Publications Dept, 2008)
    Shema, Efrat
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    Tirosh, Itay
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    Aylon, Yael
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    Huang, Jing
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    Ye, Chaoyang
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    Moskovits, Neta
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    Raver-Shapira, Nina
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    Minsky, Neri
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    Pirngruber, Judith
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    Tarcic, Gabi
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    Hublarova, Pavla
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    Moyal, Lilach
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    Gana-Weisz, Mali
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    Shiloh, Yosef
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    Yarden, Yossef
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    Johnsen, Steven A.  
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    Vojtesek, Borivoj
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    Berger, Shelley L.
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    Oren, Moshe
    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.