Scientific Report
- EMBO reports (2009) 10, 894 - 900
- doi:10.1038/embor.2009.108
Published online: 3 July 2009
Subject Category:
CDK9 directs H2B monoubiquitination and controls replication-dependent histone mRNA 3'-end processing
Judith Pirngruber1,*, Andrei Shchebet1,*, Lisa Schreiber1, Efrat Shema2, Neri Minsky2,†, Rob D Chapman3, Dirk Eick3, Yael Aylon2, Moshe Oren2 & Steven A Johnsen1
- Department of Molecular Oncology, Göttingen Center for Molecular Biosciences, University of Göttingen, Ernst-Caspari-Haus, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany
- Department of Molecular Cell Biology, The Weizmann Institute of Science, POB 26, Rehovot 76100, Israel
- Institute for Clinical Molecular Biology and Tumour Genetics, Helmholtz Center for Environmental Health, Center for Integrated Protein Science (CiPSM), Marchioninistrasse 25, 81377 Munich, Germany
Correspondence to:
Steven A Johnsen,
Tel: +49 551 39 10373; Fax: +49 551 39 13713;
E-mail: sjohnse@gwdg.de
†Present address: Laboratory of Biochemistry and Molecular Biology, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
*These authors contributed equally to this work
Received 12 February 2009; Revised 9 April 2009; Accepted 20 April 2009
Abstract
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.
Keywords:
- cyclin-dependent kinase,
- histone,
- mRNA processing,
- monoubiquitination,
- RNA polymerase II C-terminal domain
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