Role of the repressor Oaf3p in the recruitment of transcription factors and chromatin dynamics during the oleate response.

Cellular responses to environmental stimuli are mediated by the co-ordinated activity of multiple control mechanisms, which result in the dynamics of cell function. Communication between different levels of regulation is central for this adaptability. The present study focuses on the interplay between transcriptional regulators and chromatin modifiers to co-operatively regulate transcription in response to a fatty acid stimulus. The genes involved in the β-oxidation of fatty acids are highly induced in response to fatty acid exposure by four gene-specific transcriptional regulators, Oaf (oleate-activated transcription factor) 1p, Pip2p (peroxisome induction pathway 2), Oaf3p and Adr1p (alcohol dehydrogenase regulator 1). In the present study, we examine the interplay of these factors with Htz1p (histone variant H2A.Z) in regulating POT1 (peroxisomal oxoacyl thiolase 1) encoding peroxisomal thiolase and PIP2 encoding the autoregulatory oleate-specific transcriptional activator. Temporal resolution of ChIP (chromatin immunoprecipitation) data indicates that Htz1p is required for the timely removal of the transcriptional repressor Oaf3p during oleate induction. Adr1p plays an important role in the assembly of Htz1p-containing nucleosomes on the POT1 and PIP2 promoters. We also investigated the function of the uncharacterized transcriptional inhibitor Oaf3p. Deletion of OAF3 led to faster POT1 mRNA accumulation than in the wild-type. Most impressively, a highly protected nucleosome structure on the POT1 promoter during activation was observed in the OAF3 mutant cells in response to oleate induction.