title: Cell cycle-dependent chromatin shuttling of HBO1-JADE1 histone acetyl transferase (HAT) complex.
abstract: HAT HBO1 interacts with 2 isoforms of JADE1: JADE1S and JADE1L. JADE1 promotes acetylation of nucleosomal histones by HBO1. HBO1-JADE1 complex facilitates cell proliferation by unclear mechanisms. Here we report intracellular chromatin shuttling of HBO1-JADE1 complex during mitosis coupled to phosphorylation of JADE1. In interphase of dividing cells JADE1S was localized to the nucleus and associated with chromatin. As cells approached mitosis, specifically prophase, JADE1S dissociated from chromatin and associated with cytoplasm. JADE1S chromatin re-association began in telophase and paralleled nuclear envelope membrane reassembly. By early G₁, JADE1S was re-associated with chromatin and localized to the nucleus. Importantly, cytoplasmic but not chromatin-associated JADE1 protein was phosphorylated. Mass-Spectrometric analysis of JADE1S protein isolated from G₂/M-arrested cells identified 6 phosphorylated amino acid residues: S89, T92, S102, S121, S392, and T468, including 3 novel sites. Temporally, JADE1S phosphorylation and dephosphorylation during mitosis correlated with JADE1S chromatin dissociation and recruitment. JADE1S chromatin recruitment was accompanied by the global histone H4 acetylation. Pharmacological inhibitor of Aurora A kinase prevented JADE1S protein band shift and chromatin dissociation, suggesting regulatory function for phosphorylation. In vivo experiments supported our in vitro results. In mouse kidneys, JADE1S transiently accumulated in the cytoplasm of tubular epithelial cells during kidney regeneration. The transient increase in the number of cells with cytoplasmic JADE1S directly correlated with activation of tubular cell proliferation and inversely correlated with the number of cells with nuclear JADE1S staining, supporting biological role of HBO1-JADE1 shuttling during organ regeneration.
authors.affiliation: Department of Pathology; Boston University School of Medicine; Boston, MA USA.
authors.forename: Nirodhini S
authors.initials: NS
authors.lastname: Siriwardana
authors.affiliation: Department of Pathology; Boston University School of Medicine; Boston, MA USA.
authors.forename: Rosana
authors.initials: R
authors.lastname: Meyer
authors.affiliation: Renal Section; Department of Medicine; Boston Medical Center; Boston, MA USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Havasi
authors.affiliation: Hematology-Oncology Section; Department of Medicine; Boston University School of Medicine; Boston, MA USA.
authors.forename: Isabel
authors.initials: I
authors.lastname: Dominguez
authors.affiliation: Department of Pathology; Boston University School of Medicine; Boston, MA USA.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Panchenko
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism*; D004847:Epithelial Cells / Q000473:pathology / Q000502:physiology; D051548:Histone Acetyltransferases / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D008938:Mitosis; D046912:Multiprotein Complexes / Q000378:metabolism; D010766:Phosphorylation; D012038:Regeneration; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D002843:Chromatin; D018398:Homeodomain Proteins; C469360:JADE1 protein, human; D046912:Multiprotein Complexes; D025521:Tumor Suppressor Proteins; D051548:Histone Acetyltransferases; C496553:KAT7 protein, human
keywords: KAT7; MYST2; PHF17; chromatin shuttling; epithelial cell proliferation; phosphorylation; regeneration
references.citation: EMBO J. 1990 Oct;9(10):3163-70
references.pmid: 2209541
references.citation: Nature. 2004 Jul 15;430(6997):372-6
references.pmid: 15254542
references.citation: Cell. 2011 Aug 19;146(4):510-8
references.pmid: 21854979
references.citation: Curr Opin Genet Dev. 2004 Feb;14(1):29-36
references.pmid: 15108802
references.citation: Cancer Res. 2009 Mar 15;69(6):2663-8
references.pmid: 19276368
references.citation: Mol Cell Biol. 2000 Nov;20(22):8602-12
references.pmid: 11046155
references.citation: Annu Rev Biochem. 2002;71:333-74
references.pmid: 12045100
references.citation: Mol Cell Biol. 2006 Feb;26(3):1098-108
references.pmid: 16428461
references.citation: Sci Signal. 2011 Mar 15;4(164):rs3
references.pmid: 21406692
references.citation: Cell. 2002 Feb 22;108(4):475-87
references.pmid: 11909519
references.citation: Cell Mol Life Sci. 2013 Feb;70(4):661-87
references.pmid: 22864622
references.citation: Mol Endocrinol. 2006 Sep;20(9):2122-40
references.pmid: 16645042
references.citation: Science. 2001 Aug 10;293(5532):1074-80
references.pmid: 11498575
references.citation: EMBO J. 2013 Oct 30;32(21):2833-47
references.pmid: 24097061
references.citation: Microbiol Mol Biol Rev. 2000 Jun;64(2):435-59
references.pmid: 10839822
references.citation: Cell. 2007 Dec 14;131(6):1190-203
references.pmid: 18083107
references.citation: Sci Signal. 2010 Aug 24;3(136):ra64
references.pmid: 20736484
references.citation: Gene. 2009 May 1;436(1-2):108-14
references.pmid: 19393168
references.citation: Mol Cell Biol. 2011 Feb;31(4):845-60
references.pmid: 21149574
references.citation: J Biol Chem. 2002 Oct 18;277(42):39887-98
references.pmid: 12169691
references.citation: Annu Rev Biochem. 2001;70:81-120
references.pmid: 11395403
references.citation: J Biol Chem. 1999 Aug 13;274(33):23027-34
references.pmid: 10438470
references.citation: Nat Rev Mol Cell Biol. 2007 Apr;8(4):284-95
references.pmid: 17380162
references.citation: Cell Stem Cell. 2009 Aug 7;5(2):214-26
references.pmid: 19664995
references.citation: Mol Cell Biol. 2003 Dec;23(23):8553-2
references.pmid: 14612400
references.citation: Exp Cell Res. 1998 Nov 25;245(1):8-18
references.pmid: 9828096
references.citation: J Biol Chem. 2008 Oct 24;283(43):28817-26
references.pmid: 18684714
references.citation: Science. 1993 Dec 24;262(5142):2050-4
references.pmid: 8266103
references.citation: J Exp Clin Cancer Res. 2010 Nov 01;29:140
references.pmid: 21040551
references.citation: Bioessays. 1998 Apr;20(4):275-9
references.pmid: 9619097
references.citation: J Proteome Res. 2008 Mar;7(3):1346-51
references.pmid: 18220336
references.citation: Biochem J. 2005 Aug 15;390(Pt 1):293-302
references.pmid: 16083426
references.citation: Nat Rev Mol Cell Biol. 2009 Mar;10(3):192-206
references.pmid: 19234478
references.citation: Cell Res. 2011 Mar;21(3):381-95
references.pmid: 21321607
references.citation: Cell. 1995 Apr 7;81(1):95-105
references.pmid: 7720077
references.citation: Bioessays. 1998 Aug;20(8):615-26
references.pmid: 9780836
references.citation: J Clin Invest. 2011 Nov;121(11):4210-21
references.pmid: 22045571
references.citation: J Biol Chem. 2008 Jan 25;283(4):2265-74
references.pmid: 18029353
references.citation: Bioessays. 2000 Sep;22(9):836-45
references.pmid: 10944586
references.citation: J Virol. 2004 Nov;78(22):12566-75
references.pmid: 15507644
references.citation: Nature. 2006 Jul 6;442(7098):100-3
references.pmid: 16728977
references.citation: Development. 2012 Oct;139(20):3880-90
references.pmid: 22951641
references.citation: Mol Cell Biol. 2012 Feb;32(3):689-703
references.pmid: 22144582
references.citation: Trends Cell Biol. 2013 Apr;23(4):175-84
references.pmid: 23246430
references.citation: Mol Biol Cell. 2010 Feb 1;21(3):393-404
references.pmid: 19955211
references.citation: Annu Rev Biochem. 2011;80:473-99
references.pmid: 21529160
references.citation: J Biol Chem. 2001 May 4;276(18):15397-408
references.pmid: 11278932
references.citation: Nat Rev Genet. 2010 Aug;11(8):583-9
references.pmid: 20628351
references.citation: Cell. 2002 Nov 1;111(3):381-92
references.pmid: 12419248
references.citation: Mol Cell Biol. 2004 Mar;24(5):1884-96
references.pmid: 14966270
references.citation: J Biol Chem. 2004 Dec 31;279(53):56032-41
references.pmid: 15502158
references.citation: Am J Pathol. 2013 Jan;182(1):152-62
references.pmid: 23159946
references.citation: Mol Cell. 2010 Jan 15;37(1):57-66
references.pmid: 20129055
references.citation: Mol Cell. 2006 Jan 6;21(1):51-64
references.pmid: 16387653
references.citation: Sci Signal. 2009 Aug 18;2(84):ra46
references.pmid: 19690332
references.citation: Epigenetics Chromatin. 2013 Apr 02;6(1):6
references.pmid: 23547918
references.citation: Blood. 2011 Sep 1;118(9):2443-53
references.pmid: 21753189
references.citation: Nat Med. 2010 May;16(5):535-43, 1p following 143
references.pmid: 20436483
references.citation: Cell. 2007 Nov 16;131(4):633-6
references.pmid: 18022353
references.citation: Nat Cell Biol. 2011 Oct 09;13(11):1295-304
references.pmid: 21983563
references.citation: J Biol Chem. 2000 Nov 10;275(45):35200-8
references.pmid: 10930412
references.citation: Nat Cell Biol. 2004 Aug;6(8):721-30
references.pmid: 15247921
references.citation: Mol Cell. 2009 Jan 30;33(2):257-65
references.pmid: 19187766