The chromatin remodeling Isw1a complex is regulated by SUMOylation
- 5 October 2017
- journal article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 474 (20), 3455-3469
- https://doi.org/10.1042/bcj20170172
Abstract
The ISWI class of proteins consists of a family of chromatin remodeling ATPases that is ubiquitous in eukaryotes and predominantly functions to slide nucleosomes laterally. The yeast Saccharomyces cerevisiae Isw1 partners with several non-essential alternative subunits — Ioc2, Ioc3, or Ioc4 — to form two distinct complexes Isw1a and Isw1b. Besides its ATPase domain, Isw1 presents a C-terminal region formed by HAND, SANT, and SLIDE domains responsible for interaction with the Ioc proteins and optimal association of Isw1 to chromatin. Despite diverse studies on the functions of the Isw1-containing complexes, molecular evidence for a regulation of this chromatin remodeling ATPase is still elusive. Results presented here indicate that Isw1 is not only ubiquitylated but also strongly SUMOylated on multiple lysine residues by the redundant Siz1/Siz2 SUMO E3 ligases. However, Isw1 is a poor substrate of the Ulp1 and Ulp2 SUMO proteases, thus resulting in a high level of modification. Extensive site-directed mutagenesis allowed us to identify the major SUMOylation sites and develop a SUMO-defective mutant of Isw1. Using this molecular tool, we show that SUMOylation of Isw1 specifically facilitates and/or stabilizes its interaction with its cofactor Ioc3 and consequently the efficient recruitment of the Isw1–Ioc3 complex onto chromatin. Together these data reveal a new regulatory mechanism for this fascinating remodeling factor.This publication has 48 references indexed in Scilit:
- The ISW1 and CHD1 ATP-dependent chromatin remodelers compete to set nucleosome spacingin vivoNucleic Acids Research, 2016
- Chromatin dynamics: Interplay between remodeling enzymes and histone modificationsBiochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 2014
- Mechanisms and Functions of ATP-Dependent Chromatin-Remodeling EnzymesCell, 2013
- Genome-wide Nucleosome Specificity and Directionality of Chromatin RemodelersCell, 2012
- Diversity of operation in ATP-dependent chromatin remodelersBiochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 2011
- A Role for Snf2-Related Nucleosome-Spacing Enzymes in Genome-Wide Nucleosome OrganizationScience, 2011
- The Specificity and Topology of Chromatin Interaction Pathways in YeastMolecular Cell, 2011
- Chromatin- and Transcription-Related Factors Repress Transcription from within Coding Regions throughout the Saccharomyces cerevisiae GenomePLoS Biology, 2008
- ISWI complexes in Saccharomyces cerevisiaeBiochimica et Biophysica Acta (BBA) - Gene Structure and Expression, 2004
- Yeast Isw1p Forms Two Separable Complexes In VivoMolecular and Cellular Biology, 2003