The gene repressor complex NuRD interacts with the histone variant H3.3 at promoters of active genes
- Daniel C. Kraushaar1,3,4,
- Zuozhou Chen2,3,
- Qingsong Tang1,
- Kairong Cui1,
- Junfang Zhang2 and
- Keji Zhao1
- 1Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA;
- 2Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources (Shanghai Ocean University), Ministry of Education; International Research Center for Marine Biosciences at Shanghai Ocean University, Ministry of Science and Technology; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai 201306, China
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↵3 These authors contributed equally to this work.
Abstract
The histone variant H3.3 is deposited across active genes, regulatory regions, and telomeres. It remains unclear how H3.3 interacts with chromatin modifying enzymes and thereby modulates gene activity. In this study, we performed a co-immunoprecipitation-mass spectrometry analysis of proteins associated with H3.3-containing nucleosomes and identified the nucleosome remodeling and deacetylase complex (NuRD) as a major H3.3-interactor. We show that the H3.3-NuRD interaction is dependent on the H3.3 lysine 4 residue and that NuRD binding occurs when lysine 4 is in its unmodified state. The majority of NuRD binding colocalizes with H3.3 and directly correlates with gene activity. H3.3 depletion led to reduced levels of NuRD at sites previously occupied by H3.3, as well as a global decrease in histone marks associated with gene activation. Our results demonstrate the importance of H3.3 in the maintenance of the cellular epigenetic landscape and reveal a highly prevalent interaction between the histone variant H3.3 and the multiprotein complex NuRD.
Footnotes
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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.236224.118.
- Received February 20, 2018.
- Accepted September 13, 2018.
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