title: Recruitment of SWI/SNF complex is required for transcriptional activation of the SLC11A1 gene during macrophage differentiation of HL-60 cells.
abstract: The solute carrier family 11 member 1 (SLC11A1) gene is strictly regulated and exclusively expressed in myeloid lineage cells. However, little is known about the transcriptional regulation of the SLC11A1 gene during myeloid development. In this study, we used HL-60 cells as a model to investigate the regulatory elements/factors involved in the transactivation of the SLC11A1 gene during phorbol 12-myristate 13-acetate (PMA)-induced macrophage differentiation of HL-60 cells. Promoter deletion analysis showed that a 7-base AP-1-like element (TGACTCT) was critical for the responsiveness of the SLC11A1 promoter to PMA. Stimulation by PMA induced the binding of ATF-3 and the recruitment of two components of the SWI/SNF complex, BRG1 and β-actin, to this element in an ATF-3-dependent manner. RNAi-mediated depletion of ATF-3 or BRG1 markedly decreased SLC11A1 gene expression and its promoter activity induced by PMA. Luciferase reporter experiments demonstrated that ATF-3 cooperated with BRG1 and β-actin to activate the SLC11A1 promoter. Furthermore, we showed that PMA can induce the proximal (GT/AC)(n) repeat sequence to convert to the Z-DNA structure in the SLC11A1 gene promoter, and depletion of BRG1 resulted in a significant decrease of Z-DNA formation. Our results demonstrated that recruitment of the SWI/SNF complex initiated Z-DNA formation and subsequently helped to transactivate the SLC11A1 gene.
authors.affiliation: Division of Experimental Medicine, Department of Medicine, Montreal General Hospital Research Institute, McGill University, Montreal, Quebec H3G 1A4, Canada.
authors.forename: Yong Zhong
authors.initials: YZ
authors.lastname: Xu
authors.forename: Thusanth
authors.initials: T
authors.lastname: Thuraisingam
authors.forename: Rafael
authors.initials: R
authors.lastname: Marino
authors.forename: Danuta
authors.initials: D
authors.lastname: Radzioch
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology; D027682:Cation Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D043542:DNA, Z-Form / Q000235:genetics / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology*; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D051700:Activating Transcription Factor 3; D002273:Carcinogens; D027682:Cation Transport Proteins; D002868:Chromosomal Proteins, Non-Histone; D004265:DNA Helicases; D043542:DNA, Z-Form; D009687:Nuclear Proteins; D013755:Tetradecanoylphorbol Acetate; D014157:Transcription Factors; D000099173:Natural Resistance-associated Macrophage Protein 1; C490449:ATF3 protein, human; C445179:SWI-SNF-B chromatin-remodeling complex; C084108:SMARCA4 protein, human