title: Regulation of nucleolar chromatin by B23/nucleophosmin jointly depends upon its RNA binding activity and transcription factor UBF.
abstract: Histone chaperones regulate the density of incorporated histone proteins around DNA transcription sites and therefore constitute an important site-specific regulatory mechanism for the control of gene expression. At present, the targeting mechanism conferring this site specificity is unknown. We previously reported that the histone chaperone B23/nucleophosmin associates with rRNA chromatin (r-chromatin) to stimulate rRNA transcription. Here, we report on the mechanism for site-specific targeting of B23 to the r-chromatin. We observed that, during mitosis, B23 was released from chromatin upon inactivation of its RNA binding activity by cdc2 kinase-mediated phosphorylation. The phosphorylation status of B23 was also shown to strongly affect its chromatin binding activity. We further found that r-chromatin binding of B23 was a necessary condition for B23 histone chaperone activity in vivo. In addition, we found that depletion of upstream binding factor (UBF; an rRNA transcription factor) decreased the chromatin binding affinity of B23, which in turn led to an increase in histone density at the r-chromatin. These two major strands of evidence suggest a novel cell cycle-dependent mechanism for the site-specific regulation of histone density via joint RNA- and transcription factor-mediated recruitment of histone chaperones to specific chromosome loci.
authors: Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan.
authors: Miharu
authors: M
authors: Hisaoka
authors: Shuhei
authors: S
authors: Ueshima
authors: Kensaku
authors: K
authors: Murano
authors: Kyosuke
authors: K
authors: Nagata
authors: Mitsuru
authors: M
authors: Okuwaki
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D016203:CDC2 Protein Kinase; D002453:Cell Cycle; D002460:Cell Line; D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D018844:Cyclin-Dependent Kinases; D017931:DNA Primers / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000235:genetics / Q000502:physiology; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000090243:Nucleophosmin; D010766:Phosphorylation; D035463:Pol1 Transcription Initiation Complex Proteins / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D019926:Cyclin B; D017931:DNA Primers; D018832:Molecular Chaperones; D050505:Mutant Proteins; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D035463:Pol1 Transcription Initiation Complex Proteins; D012335:RNA, Ribosomal; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C063844:transcription factor UBF; D000090243:Nucleophosmin; D012313:RNA; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases