title: Chromatin condensation in terminally differentiating mouse erythroblasts does not involve special architectural proteins but depends on histone deacetylation.
abstract: Terminal erythroid differentiation in vertebrates is characterized by progressive heterochromatin formation and chromatin condensation and, in mammals, culminates in nuclear extrusion. To date, although mechanisms regulating avian erythroid chromatin condensation have been identified, little is known regarding this process during mammalian erythropoiesis. To elucidate the molecular basis for mammalian erythroblast chromatin condensation, we used Friend virus-infected murine spleen erythroblasts that undergo terminal differentiation in vitro. Chromatin isolated from early and late-stage erythroblasts had similar levels of linker and core histones, only a slight difference in nucleosome repeats, and no significant accumulation of known developmentally regulated architectural chromatin proteins. However, histone H3(K9) dimethylation markedly increased while histone H4(K12) acetylation dramatically decreased and became segregated from the histone methylation as chromatin condensed. One histone deacetylase, HDAC5, was significantly upregulated during the terminal stages of Friend virus-infected erythroblast differentiation. Treatment with histone deacetylase inhibitor, trichostatin A, blocked both chromatin condensation and nuclear extrusion. Based on our data, we propose a model for a unique mechanism in which extensive histone deacetylation at pericentromeric heterochromatin mediates heterochromatin condensation in vertebrate erythroblasts that would otherwise be mediated by developmentally-regulated architectural proteins in nucleated blood cells.
authors.affiliation: Biochemistry and Molecular Biology, College of Medicine, Penn State University, Hershey, PA 17033, USA.
authors.forename: Evgenya Y
authors.initials: EY
authors.lastname: Popova
authors.forename: Sharon Wald
authors.initials: SW
authors.lastname: Krauss
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Short
authors.forename: Gloria
authors.initials: G
authors.lastname: Lee
authors.forename: Jonathan
authors.initials: J
authors.lastname: Villalobos
authors.forename: Joan
authors.initials: J
authors.lastname: Etzell
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Koury
authors.forename: Paul A
authors.initials: PA
authors.lastname: Ney
authors.forename: Joel Anne
authors.initials: JA
authors.lastname: Chasis
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Grigoryev
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002645:Chickens; D002843:Chromatin / Q000378:metabolism*; D004900:Erythroblasts / Q000378:metabolism*; D005622:Friend murine leukemia virus / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D009707:Nucleosomes / Q000378:metabolism
chemical_list: D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D009707:Nucleosomes; C012589:trichostatin A; D006655:Histone Deacetylases