title: Esco1 Acetylates Cohesin via a Mechanism Different from That of Esco2.
abstract: Sister chromatid cohesion is mediated by cohesin and is essential for accurate chromosome segregation. The cohesin subunits SMC1, SMC3, and Rad21 form a tripartite ring within which sister chromatids are thought to be entrapped. This event requires the acetylation of SMC3 and the association of sororin with cohesin by the acetyltransferases Esco1 and Esco2 in humans, but the functional mechanisms of these acetyltransferases remain elusive. Here, we showed that Esco1 requires Pds5, a cohesin regulatory subunit bound to Rad21, to form cohesion via SMC3 acetylation and the stabilization of the chromatin association of sororin, whereas Esco2 function was not affected by Pds5 depletion. Consistent with the functional link between Esco1 and Pds5, Pds5 interacted exclusively with Esco1, and this interaction was dependent on a unique and conserved Esco1 domain. Crucially, this interaction was essential for SMC3 acetylation and sister chromatid cohesion. Esco1 localized to cohesin localization sites on chromosomes throughout interphase in a manner that required the Esco1-Pds5 interaction, and it could acetylate SMC3 before and after DNA replication. These results indicate that Esco1 acetylates SMC3 via a mechanism different from that of Esco2. We propose that, by interacting with a unique domain of Esco1, Pds5 recruits Esco1 to chromatin-bound cohesin complexes to form cohesion. Furthermore, Esco1 acetylates SMC3 independently of DNA replication.
authors.affiliation: Laboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan; Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Minamino
authors.affiliation: Laboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan; Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Ishibashi
authors.affiliation: Laboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan; Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan.
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Nakato
authors.affiliation: Laboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan; Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Akiyama
authors.affiliation: Laboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Laboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Laboratory of Cancer Stem Cell Biology, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan.
authors.forename: Lumi
authors.initials: L
authors.lastname: Negishi
authors.affiliation: Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), 3-8-31 Ariake Koto-Ku, Tokyo 135-8550, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Hirota
authors.affiliation: Laboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan; Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sutani
authors.affiliation: Laboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan; Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan. Electronic address: mbando@iam.u-tokyo.ac.jp.
authors.forename: Masashige
authors.initials: M
authors.lastname: Bando
authors.affiliation: Laboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan; Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan; CREST, JST, K's Gobancho, 7, Gobancho, Chiyoda-ku, Tokyo 102-0076, Japan. Electronic address: kshirahi@iam.u-tokyo.ac.jp.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Shirahige
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism*; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D002842:Chromatids / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004261:DNA Replication / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000097722:Cohesins
chemical_list: D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D011508:Chondroitin Sulfate Proteoglycans; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D000097722:Cohesins; C486457:PDS5A protein, human; C492318:SMC3 protein, human; C479413:ESCO1 protein, human