Project description:Genomic events including gene regulation and chromatin status are controlled by transcription factors. Here we report that the Hsp90 molecular chaperone broadly regulates the transcription factor protein family. Our studies identified a biphasic use of Hsp90 in which early inactivation (15 min) of the chaperone triggered a wide reduction of DNA binding events along the genome with concurrent changes to chromatin structure. Long-term loss (6 h) of Hsp90 resulted in a decline of a divergent yet overlaying pool of transcription factors that produced a distinct chromatin pattern. Although both phases involve protein folding, the early point correlated with Hsp90 acting in a late folding step that is critical for DNA binding function whereas prolonged Hsp90 inactivation led to a significant decrease in the steady-state transcription factor protein levels. Intriguingly, despite the broad chaperone-impact on a variety of transcription factors, the operational influence of Hsp90 was at the level of chromatin with only a mild effect on gene regulation. Thus, Hsp90 selectively governs the transcription factor process overseeing local chromatin structure.
Project description:Systematic investigation of transcription factor activity in the context of chromatin using massively parallel DNA binding and expression assays
Project description:These three replicates were analyzed in "Genomewide identification of Sko1 target promoters reveals a regulatory network that operates in response to osmotic stress in Saccharomyces cerevisiae. ", by Proft M, Gibbons FD, Copeland M, Roth FP, Struhl K; published in Eukaryot Cell. 2005 Aug;4(8):1343-52. A new analysis algorithm for Chip-chip data ('Chipper') is described in Genome Biology. Manuscript entitled "Chipper: discovering transcription-factor targets from chromatin immunoprecipitation microarrays using variance stabilization." by FD Gibbons, M Proft, K Struhl, and FP Roth. Accepted, no publication date as yet. Keywords: ChIP-chip
