Analysis of Jmjd6 Cellular Localization and Testing for Its Involvement in Histone Demethylation 英文参考文献.docVIP
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Analysis of Jmjd6 Cellular Localization and Testing for Its Involvement in Histone Demethylation 英文参考文献
AnalysisofJmjd6CellularLocalizationandTestingforIts
InvolvementinHistoneDemethylation
PhillipHahn1,IvonneWegener1,AlisonBurrells5,JensBo¨se1,AlexanderWolf2,ChristianErck3 ,Danica
Butler4,ChristopherJ.Schofield4,AngelikaBo¨ttger2,AndreasLengeling1,5*
1Department of Experimental Mouse Genetics, Helmholtz Centre for Infection Research, Braunschweig, Germany, 2Department of Biology II, Ludwig-Maximilians-
University, Planeeg-Martinsried, Germany, 3Synaptic Systems GmbH, Go¨ttingen, Germany, 4Chemistry Research Laboratory and the Oxford Centre for Integrative
Systems Biology, University of Oxford, Oxford, United Kingdom, 5The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin,
Midlothian,UnitedKingdom
Abstract
Background: Methylation of residues in histone tails is part of a network that regulates gene expression. JmjC domain
containingproteinscatalyzetheoxidativeremovalofmethylgroupsonhistonelysineresidues.Here,wereportstudiesto
testtheinvolvementofJumonjidomain-containingprotein6(Jmjd6)inhistonelysinedemethylation.Jmjd6hasrecently
beenshowntohydroxylateRNAsplicingfactorsandisknowntobeessentialforthedifferentiationofmultipletissuesand
cells during embryogenesis. However, there have been conflicting reports as to whether Jmjd6 is a histone-modifying
enzyme.
Methodology/PrincipalFindings:ImmunolocalizationstudiesrevealthatJmjd6isdistributedthroughoutthenucleoplasm
outside of regions containing heterochromatic DNA, with occasional localization in nucleoli. During mitosis, Jmjd6 is
excludedfromthenucleusandreappearsinthetelophaseofthecellcycle.WesternblotanalysesconfirmedthatJmjd6
formshomo-multimersofdifferentmolecularweightsinthenucleusandcytoplasm.Acomparisonofmono-,di-,andtri-
methylationstatesofH3K4,H3K9,H3K27,H3K36,andH4K20histoneresiduesinwildtypeandJmjd6-knockoutcellsindicate
thatJmjd6isnotinvolvedinthedemethylationofthesehistonelysineresidues.Thisisfurthersupportedbyoverexpression
of enzymatically active and inactive f
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