Stabilization of the promoter nucleosomes in nucleosome-free regions by the yeast Cyc8–Tup1 corepressor
- Kaifu Chen1,2,8,
- Marenda A. Wilson3,4,5,8,
- Calley Hirsch3,4,5,
- Anjanette Watson6,
- Shoudan Liang4,7,
- Yue Lu4,5,
- Wei Li1,2,9 and
- Sharon Y.R. Dent3,4,5,9
- 1Division of Biostatistics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA;
- 2Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA;
- 3Program in Genes and Development, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
- 4Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
- 5Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
- 6University of Vermont Bioinformatics Core, Burlington, Vermont 05405, USA;
- 7Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
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↵8 These authors contributed equally to this work.
Abstract
The yeast Cyc8 (also known as Ssn6)–Tup1 complex regulates gene expression through a variety of mechanisms, including positioning of nucleosomes over promoters of some target genes to limit accessibility to the transcription machinery. To further define the functions of Cyc8–Tup1 in gene regulation and chromatin remodeling, we performed genome-wide profiling of changes in nucleosome organization and gene expression that occur upon loss of CYC8 or TUP1 and observed extensive nucleosome alterations in both promoters and gene bodies of derepressed genes. Our improved nucleosome profiling and analysis approaches revealed low-occupancy promoter nucleosomes (P nucleosomes) at locations previously defined as nucleosome-free regions. In the absence of CYC8 or TUP1, this P nucleosome is frequently lost, whereas nucleosomes are gained at −1 and +1 positions, accompanying up-regulation of downstream genes. Our analysis of public ChIP-seq data revealed that Cyc8 and Tup1 preferentially bind TATA-containing promoters, which are also enriched in genes derepressed upon loss of CYC8 or TUP1. These results suggest that stabilization of the P nucleosome on TATA-containing promoters may be a central feature of the repressive chromatin architecture created by the Cyc8–Tup1 corepressor, and that releasing the P nucleosome contributes to gene activation.
Footnotes
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↵9 Corresponding authors
E-mail sroth{at}mdanderson.org
E-mail WL1{at}bcm.edu
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.141952.112.
- Received April 20, 2012.
- Accepted October 11, 2012.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/.
