May 27, 2016

Transcription factors GAF and HSF act at distinct regulatory steps to modulate stress-induced gene activation

BioRxiv : the Preprint Server for Biology
Fabiana M DuarteJohn T Lis

Abstract

The coordinated regulation of gene expression at the transcriptional level is fundamental to organismal development and homeostasis. Inducible systems are invaluable when studying transcription because the regulatory process can be triggered instantaneously, allowing the tracking of ordered mechanistic events. Here, we use Precision Run-On sequencing (PRO-seq) to examine the genome-wide Heat Shock (HS) response in Drosophila and the function of two key transcription factors on the immediate transcription activation or repression of all genes regulated by HS. We identify the primary HS response genes and the rate-limiting steps in the transcription cycle that GAGA-Associated Factor (GAF) and HS Factor (HSF) regulate. We demonstrate that GAF acts upstream of promoter-proximally paused RNA Polymerase II (Pol II) formation, likely at the step of chromatin opening, and that GAF-facilitated Pol II pausing is critical for HS activation. In contrast, HSF is dispensable for establishing or maintaining Pol II pausing, but is critical for the release of paused Pol II into the gene body at a subset of highly- activated genes. Additionally, HSF has no detectable role in the rapid HS-repression of thousands of genes.

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Mentioned in this Paper

Genome-Wide Association Study
RNA Polymerase II
Polymerase
Body Structure
Genes
Heat Shock Protein Activity
MAP3K14 wt Allele
Run-On Assays
Regulation of Biological Process
DNA-Directed RNA Polymerase

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