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Molecular and Cellular Biology, March 2009, p. 1649-1660, Vol. 29, No. 6
0270-7306/09/$08.00+0     doi:10.1128/MCB.01076-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Human SPT20-Containing SAGA Complex Plays a Direct Role in the Regulation of Endoplasmic Reticulum Stress-Induced Genes ^,

Zita Nagy,¹ Anne Riss,¹ Christophe Romier,¹ Xavier le Guezennec,² Ashok R. Dongre,³ Meritxell Orpinell,¹ Jiahuai Han,⁴ Henk Stunnenberg,² and Làszlò Tora^1*

Institut de Génétique et de Biologie Moléculaire et Cellulaire, UMR 7104 CNRS, ULP, INSERM U.964, Parc d'Innovation, 1 Rue Laurent Fries, BP 10142, 67404 Illkirch Cedex, C.U. de Strasbourg, France,¹ Department of Molecular Biology, NCMLS 274, Radboud University Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands,² Clinical Discovery, Pharmaceutical Research Institute, Bristol-Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543,³ Department of Immunology, IMM-32, the Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037⁴

Received 9 July 2008/ Returned for modification 3 September 2008/ Accepted 16 December 2008

One of the central questions in eukaryotic transcription is how activators can transmit their signal to stimulate gene expression in the context of chromatin. The multisubunit SAGA coactivator complex has both histone acetyltransferase and deubiquitination activities and remodels chromatin to allow transcription. Whether and how SAGA is able to regulate transcription at specific loci is poorly understood. Using mass spectrometry, immunoprecipitation, and Western blot analysis, we have identified human SPT20 (hSPT20) as the human homologue of the yeast Spt20 and show that hSPT20 is a bona fide subunit of the human SAGA (hSAGA; previously called TFTC/STAGA/PCAF) complex and that hSPT20 is required for the integrity of the hSAGA complex. We demonstrate that hSPT20 and other hSAGA subunits, together with RNA polymerase II, are specifically recruited to genes induced by endoplasmic reticulum (ER) stress. In good agreement with the recruitment of hSAGA to the ER stress-regulated genes, knockdown of hSTP20 hampers ER stress response. Surprisingly, hSPT20 recruitment was not observed for genes induced by another type of stress. These results provide evidence for a direct and specific role of the hSPT20-containing SAGA complex in transcriptional induction of ER stress-responsive genes. Thus, hSAGA regulates the transcription of stress-responsive genes in a stress type-dependent manner.

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* Corresponding author. Mailing address: Institut de Génétique et de Biologie Moléculaire et Cellulaire, UMR 7104 CNRS, ULP, INSERM U.964, Parc d'Innovation, 1 Rue Laurent Fries, BP 10142, 67404 Illkirch Cedex, C.U. de Strasbourg, France. Phone: 33 3 88 65 34 44. Fax: 33 38 65 32 01. E-mail: laszlo{at}igbmc.u-strasbg.fr

Published ahead of print on 29 December 2008.

Supplemental material for this article may be found at http://mcb.asm.org/.

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Molecular and Cellular Biology, March 2009, p. 1649-1660, Vol. 29, No. 6
0270-7306/09/$08.00+0     doi:10.1128/MCB.01076-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.