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  The CCR4-NOT complex contributes to repression of Major Histocompatibility Complex class II transcription

Rodríguez-Gil, A., Ritter, O., Saul, V. V., Wilhelm, J., Yang, C.-Y., Grosschedl, R., et al. (2017). The CCR4-NOT complex contributes to repression of Major Histocompatibility Complex class II transcription. Scientific Reports, 3547. doi:10.1038/s41598-017-03708-7.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0000-BF87-1 Version Permalink: https://hdl.handle.net/21.11116/0000-0007-AC9A-A
Genre: Journal Article

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https://www.nature.com/articles/s41598-017-03708-7 (Publisher version)
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Rodríguez-Gil, Alfonso1, Author
Ritter, Olesja1, Author
Saul, Vera V.1, Author
Wilhelm, Jochen1, Author
Yang, Chen-Yuan1, Author
Grosschedl, Rudolf2, Author           
Imai, Yumiko1, Author
Kuba, Keiji1, Author
Kracht, Michael 1, Author
Schmitz, M. Lienhard1, Author
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1External Organizations, ou_persistent22              
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              

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 Abstract: The multi-subunit CCR4 (carbon catabolite repressor 4)-NOT (Negative on TATA) complex serves as a central coordinator of all different steps of eukaryotic gene expression. Here we performed a systematic and comparative analysis of cells where the CCR4-NOT subunits CNOT1, CNOT2 or CNOT3 were individually downregulated using doxycycline-inducible shRNAs. Microarray experiments showed that downregulation of either CNOT subunit resulted in elevated expression of major histocompatibility complex class II (MHC II) genes which are found in a gene cluster on chromosome 6. Increased expression of MHC II genes after knock-down or knock-out of either CNOT subunit was seen in a variety of cell systems and also in naïve macrophages from CNOT3 conditional knock-out mice. CNOT2-mediated repression of MHC II genes occurred also in the absence of the master regulator class II transactivator (CIITA) and did not cause detectable changes of the chromatin structure at the chromosomal MHC II locus. CNOT2 downregulation resulted in an increased de novo transcription of mRNAs whereas tethering of CNOT2 to a regulatory region governing MHC II expression resulted in diminished transcription. These results expand the known repertoire of CCR4-NOT members for immune regulation and identify CNOT proteins as a novel group of corepressors restricting class II expression.

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Language(s): eng - English
 Dates: 2017
 Publication Status: Issued
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41598-017-03708-7
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Title: Scientific Reports
  Abbreviation : Sci. Rep.
Source Genre: Journal
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Publ. Info: London, UK : Nature Publishing Group
Pages: - Volume / Issue: - Sequence Number: - Start / End Page: 3547 Identifier: ISSN: 2045-2322
CoNE: https://pure.mpg.de/cone/journals/resource/2045-2322