title: Homodimeric PHD Domain-containing Rco1 Subunit Constitutes a Critical Interaction Hub within the Rpd3S Histone Deacetylase Complex.
abstract: Recognition of histone post-translational modifications is pivotal for directing chromatin-modifying enzymes to specific genomic regions and regulating their activities. Emerging evidence suggests that other structural features of nucleosomes also contribute to precise targeting of downstream chromatin complexes, such as linker DNA, the histone globular domain, and nucleosome spacing. However, how chromatin complexes coordinate individual interactions to achieve high affinity and specificity remains unclear. The Rpd3S histone deacetylase utilizes the chromodomain-containing Eaf3 subunit and the PHD domain-containing Rco1 subunit to recognize nucleosomes that are methylated at lysine 36 of histone H3 (H3K36me). We showed previously that the binding of Eaf3 to H3K36me can be allosterically activated by Rco1. To investigate how this chromatin recognition module is regulated in the context of the Rpd3S complex, we first determined the subunit interaction network of Rpd3S. Interestingly, we found that Rpd3S contains two copies of the essential subunit Rco1, and both copies of Rco1 are required for full functionality of Rpd3S. Our functional dissection of Rco1 revealed that besides its known chromatin-recognition interfaces, other regions of Rco1 are also critical for Rpd3S to recognize its nucleosomal substrates and functionin vivo. This unexpected result uncovered an important and understudied aspect of chromatin recognition. It suggests that precisely reading modified chromatin may not only need the combined actions of reader domains but also require an internal signaling circuit that coordinates the individual actions in a productive way.
authors.affiliation: From the Department of Molecular Biology, UT Southwestern Medical Center, Dallas, Texas 75390 and.
authors.forename: Chun
authors.initials: C
authors.lastname: Ruan
authors.affiliation: From the Department of Molecular Biology, UT Southwestern Medical Center, Dallas, Texas 75390 and.
authors.forename: Haochen
authors.initials: H
authors.lastname: Cui
authors.affiliation: From the Department of Molecular Biology, UT Southwestern Medical Center, Dallas, Texas 75390 and.
authors.forename: Chul-Hwan
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Medicine, University of California at San Diego, La Jolla, California 92093.
authors.forename: Sheng
authors.initials: S
authors.lastname: Li
authors.affiliation: From the Department of Molecular Biology, UT Southwestern Medical Center, Dallas, Texas 75390 and Bing4.Li@utsouthwestern.edu.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D008745:Methylation; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D009707:Nucleosomes; D021122:Protein Subunits; C000609641:Rco1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000123:Acetyltransferases; C428131:Eaf3 protein, S cerevisiae; C071665:RPD3 protein, S cerevisiae; D006655:Histone Deacetylases
keywords: PHD finger; chromatin; histone deacetylase (HDAC); histone modification; transcription