title: Human heterochromatin protein 1α promotes nucleosome associations that drive chromatin condensation.
abstract: HP1(Hsα)-containing heterochromatin is located near centric regions of chromosomes and regulates DNA-mediated processes such as DNA repair and transcription. The higher-order structure of heterochromatin contributes to this regulation, yet the structure of heterochromatin is not well understood. We took a multidisciplinary approach to determine how HP1(Hsα)-nucleosome interactions contribute to the structure of heterochromatin. We show that HP1(Hsα) preferentially binds histone H3K9Me3-containing nucleosomal arrays in favor of non-methylated nucleosomal arrays and that nonspecific DNA interactions and pre-existing chromatin compaction promote binding. The chromo and chromo shadow domains of HP1(Hsα) play an essential role in HP1(Hsα)-nucleosome interactions, whereas the hinge region appears to have a less significant role. Electron microscopy of HP1(Hsα)-associated nucleosomal arrays showed that HP1(Hsα) caused nucleosome associations within an array, facilitating chromatin condensation. Differential sedimentation of HP1(Hsα)-associated nucleosomal arrays showed that HP1(Hsα) promotes interactions between arrays. These strand-to-strand interactions are supported by in vivo studies where tethering the Drosophila homologue HP1a to specific sites promotes interactions with distant chromosomal sites. Our findings demonstrate that HP1(Hsα)-nucleosome interactions cause chromatin condensation, a process that regulates many chromosome events.
authors.affiliation: Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, Iowa 50011.
authors.forename: Abdelhamid M
authors.initials: AM
authors.lastname: Azzaz
authors.affiliation: Department of Biochemistry, University of Iowa, Iowa City, Iowa 52241.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Vitalini
authors.affiliation: Department of Biochemistry, University of Iowa, Iowa City, Iowa 52241.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Thomas
authors.affiliation: Department of Biochemistry, University of Iowa, Iowa City, Iowa 52241.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Price
authors.affiliation: Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, Iowa 50011.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Blacketer
authors.affiliation: Department of Biochemistry, University of Iowa, Iowa City, Iowa 52241.
authors.forename: Diane E
authors.initials: DE
authors.lastname: Cryderman
authors.affiliation: Department of Biochemistry, University of Iowa, Iowa City, Iowa 52241.
authors.forename: Luka N
authors.initials: LN
authors.lastname: Zirbel
authors.affiliation: Biology Department, University of Massachusetts, Amherst, Massachusetts 01003.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Woodcock
authors.affiliation: Department of Biochemistry, University of Iowa, Iowa City, Iowa 52241.
authors.forename: Adrian H
authors.initials: AH
authors.lastname: Elcock
authors.affiliation: Department of Biochemistry, University of Iowa, Iowa City, Iowa 52241. Electronic address: lori-wallrath@uiowa.edu.
authors.forename: Lori L
authors.initials: LL
authors.lastname: Wallrath
authors.affiliation: Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, Iowa 50011. Electronic address: knaak@iastate.edu.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Shogren-Knaak
mesh_terms: D000818:Animals; D002843:Chromatin / Q000737:chemistry*; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000235:genetics; D003198:Computer Simulation; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000737:chemistry; D006801:Humans; D008956:Models, Chemical; D009707:Nucleosomes / Q000737:chemistry*
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; D006657:Histones; D009707:Nucleosomes; D000090266:Chromobox Protein Homolog 5
keywords: Chromatin Structure; Chromosomes; DNA Binding Protein; Heterochromatin; Histone Modification