title: Histones to the cytosol: exportin 7 is essential for normal terminal erythroid nuclear maturation.
abstract: Global nuclear condensation, culminating in enucleation during terminal erythropoiesis, is poorly understood. Proteomic examination of extruded erythroid nuclei from fetal liver revealed a striking depletion of most nuclear proteins, suggesting that nuclear protein export had occurred. Expression of the nuclear export protein, Exportin 7 (Xpo7), is highly erythroid-specific, induced during erythropoiesis, and abundant in very late erythroblasts. Knockdown of Xpo7 in primary mouse fetal liver erythroblasts resulted in severe inhibition of chromatin condensation and enucleation but otherwise had little effect on erythroid differentiation, including hemoglobin accumulation. Nuclei in Xpo7-knockdown cells were larger and less dense than normal and accumulated most nuclear proteins as measured by mass spectrometry. Strikingly,many DNA binding proteins such as histones H2A and H3 were found to have migrated into the cytoplasm of normal late erythroblasts prior to and during enucleation, but not in Xpo7-knockdown cells. Thus, terminal erythroid maturation involves migration of histones into the cytoplasm via a process likely facilitated by Xpo7.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA.
authors.forename: Shilpa M
authors.initials: SM
authors.lastname: Hattangadi
authors.forename: Sandra
authors.initials: S
authors.lastname: Martinez-Morilla
authors.forename: Heide Christine
authors.initials: HC
authors.lastname: Patterson
authors.forename: Jiahai
authors.initials: J
authors.lastname: Shi
authors.forename: Karly
authors.initials: K
authors.lastname: Burke
authors.forename: Amalia
authors.initials: A
authors.lastname: Avila-Figueroa
authors.forename: Srividhya
authors.initials: S
authors.lastname: Venkatesan
authors.forename: Junxia
authors.initials: J
authors.lastname: Wang
authors.forename: Katharina
authors.initials: K
authors.lastname: Paulsen
authors.forename: Dirk
authors.initials: D
authors.lastname: Görlich
authors.forename: Maki
authors.initials: M
authors.lastname: Murata-Hori
authors.forename: Harvey F
authors.initials: HF
authors.lastname: Lodish
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004900:Erythroblasts / Q000166:cytology* / Q000378:metabolism*; D004920:Erythropoiesis / Q000235:genetics / Q000502:physiology; D055785:Gene Knockdown Techniques; D006657:Histones / Q000097:blood*; D028884:Karyopherins / Q000037:antagonists & inhibitors / Q000097:blood* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000097:blood; D020931:ran GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000097:blood* / Q000235:genetics
chemical_list: D006657:Histones; D028884:Karyopherins; D009687:Nuclear Proteins; C417256:RanGTP-binding protein 16; D020931:ran GTP-Binding Protein
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