title: Nuclear Condensation during Mouse Erythropoiesis Requires Caspase-3-Mediated Nuclear Opening.
abstract: Mammalian erythropoiesis involves chromatin condensation that is initiated in the early stage of terminal differentiation. The mechanisms of chromatin condensation during erythropoiesis are unclear. Here, we show that the mouse erythroblast forms large, transient, and recurrent nuclear openings that coincide with the condensation process. The opening lacks nuclear lamina, nuclear pore complexes, and nuclear membrane, but it is distinct from nuclear envelope changes that occur during apoptosis and mitosis. A fraction of the major histones are released from the nuclear opening and degraded in the cytoplasm. We demonstrate that caspase-3 is required for the nuclear opening formation throughout terminal erythropoiesis. Loss of caspase-3 or ectopic expression of a caspase-3 non-cleavable lamin B mutant blocks nuclear opening formation, histone release, chromatin condensation, and terminal erythroid differentiation. We conclude that caspase-3-mediated nuclear opening formation accompanied by histone release from the opening is a critical step toward chromatin condensation during erythropoiesis in mice.
authors.affiliation: Department of Pathology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Ward 3-210, Chicago, IL 60611, USA.
authors.forename: Baobing
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Ward 3-210, Chicago, IL 60611, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Mei
authors.affiliation: Center for Genetic Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Schipma
authors.affiliation: Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Eric Wayne
authors.initials: EW
authors.lastname: Roth
authors.affiliation: Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Reiner
authors.initials: R
authors.lastname: Bleher
authors.affiliation: Center for Advanced Microscopy, Nikon Imaging Center at Northwestern University, Chicago, IL 60611, USA.
authors.forename: Joshua Z
authors.initials: JZ
authors.lastname: Rappoport
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Amittha
authors.initials: A
authors.lastname: Wickrema
authors.affiliation: Department of Pathology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Ward 3-210, Chicago, IL 60611, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pathology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Ward 3-210, Chicago, IL 60611, USA. Electronic address: ji.peng@northwestern.edu.
authors.forename: Peng
authors.initials: P
authors.lastname: Ji
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D004900:Erythroblasts / Q000166:cytology*; D004920:Erythropoiesis / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008938:Mitosis / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism
chemical_list: D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; C505409:Casp3 protein, mouse; D053148:Caspase 3