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Regulation Der Genexpression in Halophilen Archaea

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Regulation Der Genexpression in Halophilen Archaea Regulation der Genexpression in halophilen Archaea Dissertation zur Erlangung des Doktorgrades der Naturwissenschaften vorgelegt beim Fachbereich Biowissenschaften der Johann Wolfgang Goethe-Universität in Frankfurt am Main eingereicht von Michael Dambeck aus Wiesbaden Frankfurt am Main, 2010 (D30) vom Fachbereich Biowissenschaften (15) der Johann Wolfgang Goethe-Universität als Dissertation angenommen. Dekan: Prof. Dr. Volker Müller Gutachter: Prof. Dr. Jörg Soppa Prof. Dr. Beatrix Süß Datum der Disputation: Aus der Arbeit hervorgegangene Veröffentlichungen: Dambeck M, Soppa J. (2008). Characterization of a Haloferax volcanii member of the enolase superfamily: deletion mutant construction, expression analysis, and transcriptome comparison. Arch Microbiol. 190(3):341-53. Soppa J, Baumann A, Brenneis M, Dambeck M, Hering O, Lange C. (2008). Genomics and functional genomics with haloarchaea. Arch Microbiol. 190(3):197-215. Johnsen U, Dambeck M, Zaiss H, Fuhrer T, Soppa J, Sauer U, Schönheit P. (2009). D-xylose degradation pathway in the halophilic archaeon Haloferax volcanii. J Biol Chem. 284(40):27290-303. Inhaltsverzeichnis 1 Zusammenfassung ............................................................................................................ 1 2 Einleitung .......................................................................................................................... 3 2.1 Archaea – die dritte Domäne des Lebens .................................................................... 3 2.2 Modellorganismus Haloferax volcanii ........................................................................ 5 2.3 Die Enolase Superfamilie ............................................................................................ 6 2.3.1 iftA – Ein Mitglied der Familie .......................................................................... 6 2.3.2 „La superfamilia“ ............................................................................................... 7 2.4 Die DNA-Architektur .................................................................................................. 7 2.4.1 DNA Wrapper .................................................................................................... 9 2.4.2 Archaeale Histone .............................................................................................. 9 2.4.3 Posttranslationale Modifikation von Histonen ................................................. 10 2.4.4 Histon Acetyltransferasen (HATs) ................................................................... 11 2.4.5 Histon Deacetylasen (HDACs) ........................................................................ 12 2.4.6 Was bisher geschah… ...................................................................................... 13 2.5 Archaeale Motilität und Chemotaxis ......................................................................... 14 2.5.1 Archaeale Flagellen .......................................................................................... 14 2.5.2 Chemotaxis ....................................................................................................... 15 2.6 Zielsetzung ................................................................................................................. 17 3 Ergebnisse ....................................................................................................................... 18 3.1 Charakterisierung von iftA ......................................................................................... 18 3.1.1 In silico Analysen zur Funktionsaufklärung .................................................... 18 3.1.2 in frame Deletionsmutante von iftA ................................................................. 20 3.1.3 Medium- und Wachstumsphasen-abhängige Expression von iftA ................... 22 3.1.4 Untersuchung des Transkriptoms in Abhängigkeit von IftA ........................... 25 3.2 Genregulation durch Protein-Acetylierung/Deacetylierung ...................................... 27 3.2.1 Charakterisierung der Histonmutanten ............................................................. 27 3.2.2 Transkriptom abhängig von Histonacetylierungen .......................................... 28 3.2.2.1 Der Acetylierte Zustand ................................................................................... 28 3.2.2.2 Der Deacetylierte Zustand ................................................................................ 31 3.2.3 Transkriptom Analysen von Acetylase- und Deacetylasemutante ................... 31 3.2.3.1 Das Pat1-abhängige Transkriptom ................................................................... 32 3.2.3.2 Das Sir2-abhängige Transkriptom ................................................................... 33 3.2.4 Sir2 – eine Klasse III Histondeacetylase (HDAC) ........................................... 38 3.2.4.1 Transkription und Translation von Sir2 ........................................................... 38 Inhaltsverzeichnis 3.2.4.2 Charakterisierung der Deletionsmutante Δsir2 ................................................ 39 3.2.4.3 Das Flagellen Gencluster ................................................................................. 44 3.2.5 Unterssuchung der Chemotaxis in H. volcanii ................................................. 45 3.2.5.1 „Chemical-in-plug“ Assay ............................................................................... 45 3.2.5.2 Kapillar Assay .................................................................................................. 46 4 Diskussion ....................................................................................................................... 48 4.1.1 IftA und die Enolase Superfamilie ................................................................... 48 4.1.2 Proteinacetylierung/-deacetylierung und Histone ............................................ 53 4.1.2.1 Sir2, Motilität und Chemotaxis – Theorie... ..................................................... 58 4.1.2.2 Sir2, Motilität und Chemotaxis – ...und Praxis ................................................ 60 4.1.2.3 Regulation der Transkription – Pat1, Sir2 und das Histon ............................... 63 5 Material und Methoden ................................................................................................. 64 5.1 Materialien ................................................................................................................. 64 5.1.1 Laborgeräte ....................................................................................................... 64 5.1.2 Chemikalien ..................................................................................................... 65 5.1.3 Verbrauchsmaterialien ..................................................................................... 66 5.1.4 Enzyme ............................................................................................................. 66 5.1.5 Antikörper ........................................................................................................ 67 5.1.6 Größenstandards ............................................................................................... 67 5.1.7 System-Kits ...................................................................................................... 67 5.1.8 Plasmide ........................................................................................................... 68 5.1.9 Oligonukleotide ................................................................................................ 69 5.2 Organismen und Zellzucht ......................................................................................... 70 5.2.1 Organismen ...................................................................................................... 70 5.2.2 Nährmedien und Zellkultivierung .................................................................... 71 5.2.3 Stammhaltung ................................................................................................... 74 5.2.4 Bestimmung der Zelldichte .............................................................................. 75 5.2.5 Methoden zur Untersuchung der Chemotaxis .................................................. 75 5.2.5.1 Allgemeine Vorbereitungen ............................................................................. 75 5.2.5.2 „Chemical-in-Plug“ Methode ........................................................................... 76 5.2.5.3 Kapillar Assay .................................................................................................. 76 5.3 Molekularbiologische Methoden ............................................................................... 78 5.3.1 Isolierung von Plasmid-DNA aus E. coli ......................................................... 78 5.3.2 Isolierung von genomischer DNA aus H. volcanii .......................................... 79 5.3.3 Isolierung von Gesamt-RNA aus H. volcanii ................................................... 80 Inhaltsverzeichnis 5.3.4 Reinigung von Nukleinsäuren .......................................................................... 81 5.3.5 Phenol/Chloroform Extraktion ......................................................................... 81 5.3.6 Konzentrationsbestimmung von Nukleinsäurelösungen .................................. 82 5.3.7 Elektrophoretische Auftrennung von DNA-Lösungen..................................... 82 5.3.8 Elektrophoretische Auftrennung von RNA-Lösungen ....................................
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