In eukaryotic cells, the Ccr4–Not complex can regulate mRNA metabolism at various levels. Previously, we showed that promoter targeting of the CNOT2 subunit resulted in strong repression of RNA polymerase II transcription, which was sensitive to the HDAC (histone deacetylase) inhibitor, trichostatin A [Zwartjes, Jayne, van den Berg and Timmers (2004) J. Biol. Chem. 279, 10848–10854]. In the present study, the cofactor requirement for CNOT2-mediated repression was investigated. We found that coexpression of SMRT (silencing mediator for retinoic acid receptor and thyroid-hormone receptor) or NCoR (nuclear hormone receptor co-repressor) in combination with HDAC3 (or HDAC5 and HDAC6) augmented the repression by CNOT2. This repressive effect is mediated by the conserved Not-Box, which resides at the C-terminus of CNOT2 proteins. We observed physical interactions of CNOT2 with several subunits of the SMRT/NCoR–HDAC3 complex. Our results show that the SMRT/NCoR–HDAC3 complex is a cofactor of CNOT2-mediated repression and suggest that transcriptional regulation by the Ccr4–Not complex involves regulation of chromatin modification.
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Research Article|
August 29 2006
Involvement of the SMRT/NCoR–HDAC3 complex in transcriptional repression by the CNOT2 subunit of the human Ccr4–Not complex
Sandrine Jayne;
Sandrine Jayne
1
1Department of Physiological Chemistry, Stratenum STR 3.211, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
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Carin G. M. Zwartjes;
Carin G. M. Zwartjes
1Department of Physiological Chemistry, Stratenum STR 3.211, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
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Frederik M. A. Van Schaik;
Frederik M. A. Van Schaik
1Department of Physiological Chemistry, Stratenum STR 3.211, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
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H. Th. Marc Timmers
H. Th. Marc Timmers
2
1Department of Physiological Chemistry, Stratenum STR 3.211, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
2To whom correspondence should be addressed (email h.t.m.timmers@med.uu.nl).
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Publisher: Portland Press Ltd
Received:
March 15 2006
Revision Received:
May 16 2006
Accepted:
May 19 2006
Accepted Manuscript online:
May 19 2006
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2006
Biochem J (2006) 398 (3): 461–467.
Article history
Received:
March 15 2006
Revision Received:
May 16 2006
Accepted:
May 19 2006
Accepted Manuscript online:
May 19 2006
Citation
Sandrine Jayne, Carin G. M. Zwartjes, Frederik M. A. Van Schaik, H. Th. Marc Timmers; Involvement of the SMRT/NCoR–HDAC3 complex in transcriptional repression by the CNOT2 subunit of the human Ccr4–Not complex. Biochem J 15 September 2006; 398 (3): 461–467. doi: https://doi.org/10.1042/BJ20060406
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