Mechanismen zur Steuerung transkriptioneller Programme für Wachstum und Differenzierung durch den TEA-Regulator Tec1 in Saccharomyces cerevisiae

Die Koordination von Wachstum und Differenzierung als Antwort auf verschiedene Signale und Umweltbedingungen ist eine grundlegende Eigenschaft von Organismen. Hierbei erfordern die Anpassung von Zellteilungszyklus und Stoffwechsel und morphologische Änderungen eine spezifische Regulation der Genexp...

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Bibliographic Details
Main Author: van der Felden, Julia
Contributors: Mösch, Hans-Ulrich (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2012
Online Access:PDF Full Text
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The coordination of cellular growth and differentiation in response to internal and external signals is an elementary feature of all organisms. Adaptation of cell division cycle, metabolism and morphological alterations require a specific regulation of gene expression executed by transcription factors. In many cases, it is not known which transcription factors are located at target promoters during control of growth and division. Using the paradigm of combinatorial and promoter-specific control of the TEA-family transcription factor Tec1 from the baker´s yeast Saccharomyces cerevisiae, this work targets to answer this question. Tec1 is controlled by the Fus3/Kss1 MAPK signaling pathway and regulates the cellular differentiation programs biofilm formation and conjugation together with the transcription factor Ste12. In the first part of this work, the Tec1-Ste12 complex formation was investigated in detail. The results show that Ste12-dependent and Ste12-independent Tec1 target genes can be divided into different classes. Moreover, Ste12 controls Tec1 protein stability via the Tec1-C-terminus by which Tec1 is also able to activate Ste12-independent target gene expression. In the second part of this work, two novel interaction partners of Tec1, the co-regulators Msa1 and Msa2 were identified. Tec1, Msa1 and Msa2 co-regulate the differentiation programs biofilm formation and conjugation. Moreover, these proteins control cellular growth and correspondingly cell size by affecting cell cycle and ribosome biogenesis. Tec1, Ste12, Msa1 and Msa2 can form several distinct complexes that bind to promoters of co-regulated genes. In the third part, an in vivo system for quantitative analysis of Fus3/Kss1 MAPK signaling dynamics was established and validated under different conditions. With this system the concentration, localization and program-specific activity of the regulators Tec1, Ste12, Dig1 and Dig2 can be determined by fluorescence microscopy.