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

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...

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Autores principales:	Alfonso Rodríguez-Gil, Olesja Ritter, Vera V. Saul, Jochen Wilhelm, Chen-Yuan Yang, Rudolf Grosschedl, Yumiko Imai, Keiji Kuba, Michael Kracht, M. Lienhard Schmitz
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/81adf3881fe34ca59260aca570cca7b7
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spelling	oai:doaj.org-article:81adf3881fe34ca59260aca570cca7b72021-12-02T12:30:17ZThe CCR4-NOT complex contributes to repression of Major Histocompatibility Complex class II transcription10.1038/s41598-017-03708-72045-2322https://doaj.org/article/81adf3881fe34ca59260aca570cca7b72017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03708-7https://doaj.org/toc/2045-2322Abstract 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.Alfonso Rodríguez-GilOlesja RitterVera V. SaulJochen WilhelmChen-Yuan YangRudolf GrosschedlYumiko ImaiKeiji KubaMichael KrachtM. Lienhard SchmitzNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alfonso Rodríguez-Gil Olesja Ritter Vera V. Saul Jochen Wilhelm Chen-Yuan Yang Rudolf Grosschedl Yumiko Imai Keiji Kuba Michael Kracht M. Lienhard Schmitz The CCR4-NOT complex contributes to repression of Major Histocompatibility Complex class II transcription
description	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.
format	article
author	Alfonso Rodríguez-Gil Olesja Ritter Vera V. Saul Jochen Wilhelm Chen-Yuan Yang Rudolf Grosschedl Yumiko Imai Keiji Kuba Michael Kracht M. Lienhard Schmitz
author_facet	Alfonso Rodríguez-Gil Olesja Ritter Vera V. Saul Jochen Wilhelm Chen-Yuan Yang Rudolf Grosschedl Yumiko Imai Keiji Kuba Michael Kracht M. Lienhard Schmitz
author_sort	Alfonso Rodríguez-Gil
title	The CCR4-NOT complex contributes to repression of Major Histocompatibility Complex class II transcription
title_short	The CCR4-NOT complex contributes to repression of Major Histocompatibility Complex class II transcription
title_full	The CCR4-NOT complex contributes to repression of Major Histocompatibility Complex class II transcription
title_fullStr	The CCR4-NOT complex contributes to repression of Major Histocompatibility Complex class II transcription
title_full_unstemmed	The CCR4-NOT complex contributes to repression of Major Histocompatibility Complex class II transcription
title_sort	ccr4-not complex contributes to repression of major histocompatibility complex class ii transcription
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/81adf3881fe34ca59260aca570cca7b7
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The CCR4-NOT complex contributes to repression of Major Histocompatibility Complex class II transcription

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