Involvement of the SMRT/NCoR-HDAC3 complex in transcriptional repression by the CNOT2 subunit of the human Ccr4-Not complex

Sandrine Jayne , Carin G.M. Zwartjes , Frederik M.A. van Schaik , H.Th. Marc Timmers , H.Th. Marc Timmers (1)

1 Department of Physiological Chemistry

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 histone deacetylase (HDAC) inhibitor, trichostatin A. In this study, the cofactor requirement for CNOT2-mediated repression was investigated. We found that coexpression of SMRT or NCoR in combination with HDAC3 (or HDAC5 and HDAC6) augmented 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.

Mots clés: Life Sciences

Sandrine Jayne, Carin G.M. Zwartjes, Frederik M.A. van Schaik, H.Th. Marc Timmers, H.Th. Marc Timmers. Involvement of the SMRT/NCoR-HDAC3 complex in transcriptional repression by the CNOT2 subunit of the human Ccr4-Not complex. Biochemical Journal, 2006, 398 (3), pp.461-467. ⟨10.1042/BJ20060406⟩. ⟨hal-00478554⟩