Zaucker, Andreas (2011)
Ph.D. thesis, University of Birmingham.
Replacement of the prototype promoter recognition factor (PRF) TFIID by alternative PRFs or changes in its subunit composition have recently been implicated in differentiation processes during development. TFIID is composed of TBP (TATA-binding protein) and 13 TAFs (TBP-associated factors). I comprehensively studied the roles of Tafs during vertebrate development using zebrafish model.
Taf knock down (kd) phenotypes generated in an antisense morpholino oligonucleotide (MO) screen suggest differential functions of Tafs during zebrafish development. The kd phenotypes also propose a special requirement of DNA-binding Tafs during zebrafish development.
In conjunction with zygotic mutant phenotype analysis of zebrafish taf8-mutants compared to taf6-mutants I investigated a potential coactivator function of Taf8 for Pparγ, which has been suggested by in vitro data. Oil Red O (ORO) stainings of 5 dpf (days post fertilisation) taf8- and taf6-mutant larvae revealed a specific lipogenesis defect in liver and intestine of taf8-mutant larvae. The results from treatments with a PPARγ inhibitor suggest that this lipogenic process is Pparγ-dependent. To convincingly establish a coactivator function of Taf8 for Pparγ during early zebrafish development, future work has to link the 5 dpf lipogenesis phenotype of taf8-mutants to defects in Pparγ-dependent transcription.
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