title: PINK1 regulates histone H3 trimethylation and gene expression by interaction with the polycomb protein EED/WAIT1.
abstract: Mutations in PTEN-induced putative kinase 1 (PINK1) gene are associated to early-onset recessive forms of Parkinson disease. PINK1 function is related to mitochondria homeostasis, but the molecular pathways in which PINK1 is involved are largely unknown. Here, we report the identification of the embryonic ectoderm development polycomb histone-methylation modulator (EED/WAIT1) as a PINK1-interacting and -regulated protein. The PINK1:EED/WAIT1 physical interaction was mediated by the PINK1 kinase domain and the EED/WAIT1 40 amino acid ending with tryptophan and aspartate (WD40)-repeat region, and PINK1 phosphorylated EED/WAIT1 in vitro. PINK1 associated with EED/WAIT1 in cells and relocated EED/WAIT1 to the mitochondria. This interaction reduced the trimethylation of lysine 27 from histone H3, which affected polycomb-regulated gene transcription during RA differentiation of SH-SY5Y human neuroblastoma cells. Our findings unveil a pathway by which PINK1 regulates histone methylation and gene expression through the polycomb repressor complex.
authors: Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas, 46010 Valencia, Spain. aberthier@ibv.csic.es
authors: Arnaud
authors: A
authors: Berthier
authors: Judit
authors: J
authors: Jiménez-Sáinz
authors: Rafael
authors: R
authors: Pulido
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001665:Binding Sites / Q000235:genetics; D019556:COS Cells; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008928:Mitochondria / Q000378:metabolism; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000494:pharmacology; D020798:Two-Hybrid System Techniques; D000099202:PTEN-Induced Putative Kinase
chemical_list: D000970:Antineoplastic Agents; D006657:Histones; D008239:Lysine; D063151:Polycomb Repressive Complex 2; D011494:Protein Kinases; D014212:Tretinoin; D000099202:PTEN-Induced Putative Kinase; C491488:EED protein, human
keywords: apoptosis; cell differentiation
references: J Biol Chem. 1998 Oct 16;273(42):27459-66
references: 9765275
references: FEBS Lett. 2011 Jul 7;585(13):2067-77
references: 21575638
references: Mol Endocrinol. 2005 Mar;19(3):563-73
references: 15677708
references: J Neurosci. 2007 Feb 21;27(8):1868-78
references: 17314283
references: Stem Cells. 2007 Sep;25(9):2191-9
references: 17525233
references: Proc Natl Acad Sci U S A. 2011 Jun 7;108(23):9572-7
references: 21606348
references: Eur J Cancer. 1995;31A(4):453-8
references: 7576944
references: J Mol Biol. 2007 Dec 14;374(5):1145-57
references: 17997413
references: Nat Cell Biol. 2007 Nov;9(11):1243-52
references: 17906618
references: Genetics. 1998 Oct;150(2):613-32
references: 9755194
references: Structure. 2007 Oct;15(10):1306-15
references: 17937919
references: Int J Biochem Cell Biol. 2011 Apr;43(4):474-7
references: 21241820
references: Biochemistry. 2009 Mar 10;48(9):2045-52
references: 19152501
references: PLoS Biol. 2007 Jul;5(7):e172
references: 17579517
references: Cell Death Dis. 2011 Sep 01;2:e204
references: 21881606
references: Ann Neurol. 2006 Oct;60(4):389-98
references: 17068789
references: Connect Tissue Res. 2008;49(3):197-202
references: 18661342
references: Nat Rev Mol Cell Biol. 2009 Oct;10(10):697-708
references: 19738629
references: J Biol Chem. 2011 Mar 4;286(9):7182-9
references: 21177249
references: Genes Dev. 2006 May 1;20(9):1123-36
references: 16618801
references: J Neurosci. 2008 Aug 13;28(33):8199-207
references: 18701682
references: Nature. 2011 Jan 20;469(7330):343-9
references: 21248841
references: Biochem Biophys Res Commun. 2009 Jun 5;383(3):331-5
references: 19358826
references: J Neurochem. 2009 Mar;108(6):1561-74
references: 19166511
references: Hum Mol Genet. 2010 Jan 15;19(2):352-63
references: 19880420
references: Biochem Biophys Res Commun. 2008 Dec 19;377(3):975-80
references: 18957282
references: Mol Cell. 2009 Mar 13;33(5):627-38
references: 19285945
references: Cell Death Differ. 2006 May;13(5):852-60
references: 16397579
references: Cell Signal. 2012 Feb;24(2):577-587
references: 22036806
references: Mol Cell. 2004 Apr 23;14(2):183-93
references: 15099518
references: J Neurochem. 2008 Apr;105(1):18-33
references: 18221368
references: Hum Pathol. 2011 Jan;42(1):75-87
references: 20971498
references: Dev Biol. 2012 Jul 15;367(2):91-9
references: 22565092
references: Biochem Biophys Res Commun. 2005 Jul 1;332(2):622-32
references: 15896722
references: Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):12022-7
references: 18687899
references: Clin Cancer Res. 2011 May 1;17(9):2613-8
references: 21367748
references: Acta Neuropathol. 2012 Feb;123(2):173-88
references: 22057787
references: J Chem Neuroanat. 2011 Mar;41(2):73-85
references: 21126574
references: Antioxid Redox Signal. 2011 May 15;14(10):1929-38
references: 21194381
references: EMBO J. 2001 Dec 17;20(24):7209-19
references: 11742997
references: Science. 2013 Apr 26;340(6131):471-5
references: 23620051
references: Mol Cell Biol. 1997 Nov;17(11):6663-72
references: 9343430
references: Science. 2004 May 21;304(5674):1158-60
references: 15087508
references: Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1716-21
references: 18218782
references: Development. 1998 Sep;125(17):3483-96
references: 9693151
references: Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5703-8
references: 15824318
references: Mol Cell. 2004 Jan 30;13(2):179-90
references: 14759364
references: Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1:S66-70
references: 22166458
references: Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):378-83
references: 19966284