Endoplasmic Reticulum Stress-Responsive Transcription Factor ATF6α Directs Recruitment of the Mediator of RNA Polymerase II Transcription and Multiple Histone Acetyltransferase Complexes

Sela D, Chen L, Martin-Brown S, Washburn MP, Florens L, Conaway JW, Conaway RC.
J. Biol Chem
Abstract The basic-leucine zipper transcription factor ATF6α functions as a master regulator of endoplasmic reticulum (ER) stress response genes. Previous studies have established that, in response to ER stress, ATF6α translocates to the nucleus and activates transcription of ER stress response genes upon binding sequence-specifically to ER stress response enhancer elements (ERSEs) in their promoters. In this report, we investigate the biochemical mechanism by which ATF6α activates transcription. By exploiting a combination of biochemical and MudPIT-based mass spectrometry approaches, we have obtained evidence that ATF6α functions at least in part by recruiting to the ERSEs of ER stress response genes a collection of RNA polymerase II (Pol II) coregulatory complexes, including the Mediator and multiple histone acetyltransferase complexes, among which are the Spt-Ada-Gcn5 Acetyl-transferase (SAGA) and Ada-Two-A-Containing (ATAC) complexes. Our findings shed new light on the mechanism of action of ATF6α, and they outline a straightforward strategy for applying MudPIT mass spectrometry to determine which Pol II transcription factors and coregulators are recruited to promoters and other regulatory elements to control transcription.