title: CBF/NF-Y controls endoplasmic reticulum stress induced transcription through recruitment of both ATF6(N) and TBP.
abstract: Previously the analysis of promoters regulated by endoplasmic reticulum (ER) stress identified a composite promoter element, ERSE that interacts with both CBF/NF-Y (CBF) and ATF6(N) transcription factors. This prompted us to investigate the underlying mechanism by which CBF, a ubiquitously binding transcription factor, specifically controls transcription activation during ER stress. The in vitro DNA binding study performed using purified recombinant proteins revealed that CBF specifically recruits ATF6(N) to ERSE DNA but it does not interact with ATF6(N) in absence of DNA binding. Inhibition of CBF binding resulted in a significant reduction of optimal transcription activation of cellular genes during ER stress. Analysis of cellular promoters by ChIP demonstrated that CBF is needed for recruitment of both ATF6(N) and TBP but not for either acetylation of histone H3-K9 or trimethylation of histone H3-K4 during ER stress. Together these study results reveal that CBF controls ER stress-inducible transcription through recruitment of both ATF6(N) and TBP but not through chromatin modifications. Our observations are in agreement with the results of recently published studies that have shown that CBF controls transcription of varieties of inducible promoters through recruitment of general transcription factors but not through acetylation of histone H4. These findings provide a paradigm of the function of CBF in inducible transcription.
authors.affiliation: Department of Molecular Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Luo
authors.forename: Jing-Fang
authors.initials: JF
authors.lastname: Lu
authors.forename: Qianghua
authors.initials: Q
authors.lastname: Hu
authors.forename: Sankar N
authors.initials: SN
authors.lastname: Maity
mesh_terms: D051702:Activating Transcription Factor 6 / Q000378:metabolism*; D001483:Base Sequence; D023081:CCAAT-Binding Factor / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000473:pathology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D035181:TATA-Box Binding Protein / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D051702:Activating Transcription Factor 6; D023081:CCAAT-Binding Factor; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D035181:TATA-Box Binding Protein; D004247:DNA