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CDK9 directs H2B monoubiquitination and controls replication-dependent histone mRNA 3'-end processing.


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.

SUBMITTER: Pirngruber J 

PROVIDER: S-EPMC2726677 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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CDK9 directs H2B monoubiquitination and controls replication-dependent histone mRNA 3'-end processing.

Pirngruber Judith J   Shchebet Andrei A   Schreiber Lisa L   Shema Efrat E   Minsky Neri N   Chapman Rob D RD   Eick Dirk D   Aylon Yael Y   Oren Moshe M   Johnsen Steven A SA  

EMBO reports 20090703 8


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 monoub  ...[more]

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