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.

Highlights

  • The human promyelocytic leukemia cell line HL-60 has been shown to be a useful model to study the regulation of SLC11A1 gene expression

  • We found that the SWI/SNF complex is recruited to this element via interaction with transcriptional factor ATF-3 and is required for phorbol 12-myristate 13-acetate (PMA)-induced activation of human SLC11A1 gene transcription

  • Our results demonstrate that PMA can induce the Z-DNA formation in the SLC11A1 gene promoter and that BRG1 is essential during this process

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Summary

Introduction

Our previous study demonstrated that during PMA-induced differentiation of HL-60 cells toward macrophages, nuclear ␤-actin and RNA polymerase II are recruited to the SLC11A1 promoter and are involved in the transcriptional activation of the SLC11A1 gene [47]. We found that the SWI/SNF complex is recruited to this element via interaction with transcriptional factor ATF-3 and is required for PMA-induced activation of human SLC11A1 gene transcription.

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