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Endoplasmic Reticulum Stress-responsive Transcription Factor ATF6α Directs Recruitment of the Mediator of RNA Polymerase II Transcription and Multiple Histone Acetyltransferase Complexes
Sela, Dotan Martin-Brown, Skylar Washburn, Michael P. Florens, Laurence Conaway, Joan Weliky Conaway, Ronald C.
Sela, Dotan
Martin-Brown, Skylar
Washburn, Michael P.
Florens, Laurence
Conaway, Joan Weliky
Conaway, Ronald C.
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Journal article
Date
2012-05-10
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Committee member
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Cancer and Cellular Biology
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https://doi.org/10.1074/jbc.M112.369504
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 in their promoters. In this study, we investigate the biochemical mechanism by which ATF6α activates transcription. By exploiting a combination of biochemical and multidimensional protein identification technology-based mass spectrometry approaches, we have obtained evidence that ATF6α functions at least in part by recruiting to the ER stress response enhancer elements of ER stress response genes a collection of RNA polymerase II coregulatory complexes, including the Mediator and multiple histone acetyltransferase complexes, among which are the Spt-Ada-Gcn5 acetyltransferase (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 multidimensional protein identification technology mass spectrometry to determine which RNA polymerase II transcription factors and coregulators are recruited to promoters and other regulatory elements to control transcription. Background: Transcription factor ATF6α is a master regulator of genes induced by endoplasmic reticulum stress. Results: ATF6α can recruit Mediator and histone acetyltransferase complexes to promoter DNA via interactions with overlapping sites in the activation domain of ATF6α. Conclusion: ATF6α sequences essential for gene activation recruit Mediator and histone acetyltransferases. Significance: Learning how coregulators communicate with DNA binding transcription factors is important for understanding gene regulation.
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Citation
Sela D, Chen L, Martin-Brown S, Washburn MP, Florens L, Conaway JW, Conaway RC. Endoplasmic Reticulum Stress-responsive Transcription Factor ATF6α Directs Recruitment of the Mediator of RNA Polymerase II Transcription and Multiple Histone Acetyltransferase Complexes. J. Biol. Chem. 2012 May 10;287(27):23035-23045. doi:10.1074/jbc.M112.369504.
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Elsevier
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Journal of Biological Chemistry, Vol. 268, Iss. 13
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