The unfolding SAGA of transcriptional co-activators

Successful gene expression requires the concerted action of a horde of gene regulatory factors. Long overshadowed by bonafide transcription factors, co­activators, the hangers-on that facilitate transcription by docking onto transcription factors or modifying DNA packaging, have recently come to the fore. The highly conserved co-activator SAGA, short for Spt-Ada-Gcn5-Acetyl transferase, is one of them.

Best known for lending a helping hand during the early steps of transcriptional initiation in yeast, a collaboration between Stowers researchers Susan Abmayr, PhD, and Jerry Workman, PhD, uncovered that SAGA also plays an important role in tissue-­specific gene expression in fruit flies. When Senior Research Associate Vikki Weake, PhD, who led the study, determined the composition and localization of the SAGA complex in muscle and neuronal cells of late stage embryos of the fruit fly Drosophila, she found that SAGA was associated with considerably more transcription factors in muscle compared to neurons.

In an unexpected twist, the team detected SAGA together with polymerase as the promoters of genes that appear not to be transcribed and that therefore may contain a paused, or stalled, polymerase. Paused RNA polymerase II, preloaded at the transcription start site and ready to go at a moment's notice, is often found on developmentally regulated genes.

"Pausing is not as prevalent in yeast as it is in multi-cellular organisms,'' explains Workman. "It allows genes to be synchronously and uniformly induced. The presence of SAGA with polymerase that has initiated transcription but is paused prior to elongation suggests a prominent function for SAGA in orchestrating tissue-specific gene expression."

The study was published in the July 15, 2011, issue of Genes & Development.