SRG3, a mouse homolog of yeast SWI3 and human BAF155, is known to be a core component of SWI/SNF chromatin-remodeling complex. We have previously shown that SRG3 plays essential roles in early mouse embryogenesis, brain development, and T-cell development. SRG3 gene expression was differentially regulated depending on the developmental stages and exhibited tissue-specific pattern. In this study, we showed that the functional interactions between Sp and Ets family transcription factors are crucial for the SRG3 expression. Sp1 and Sp3 specifically bound to the two canonical Sp-binding sites (GC boxes) at -152 and -114, and a non-canonical Sp-binding site (CCTCCT motif) at -108 in the SRG3 promoter. Using Drosophila SL2 cells, we found that various Sp or Ets family members activate the SRG3 promoter through these Sp- or Ets-binding sites, respectively, in a dose-dependent manner. Intriguingly, different combinatorial expression of Ets and Sp factors in SL2 cells resulted in either strong synergistic activation or repression of the SRG3 promoter activity. Moreover, the Sp-mediated activation of SRG3 promoter required the intact Ets-binding element. Taken together, these results suggest that diverse interactions between Sp1/Sp3 and Ets factors are crucial for the SRG3 gene expression.
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http://dx.doi.org/10.1016/j.bbrc.2005.10.107 | DOI Listing |
Int J Mol Sci
October 2024
Department of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, Seoul 05006, Republic of Korea.
The SWItch3-related gene (SRG3) is a core component of ATP-dependent SWI/SNF complexes, which are crucial for regulating immune cell development and function (e.g., macrophages and CD4 T cells), embryonic development, and non-immune cell differentiation.
View Article and Find Full Text PDFInt J Mol Sci
March 2021
Department of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, Seoul 05006, Korea.
We previously showed that ubiquitous overexpression of the chromatin remodeling factor SWItch3-related gene (SRG3) promotes M2 macrophage differentiation, resulting in anti-inflammatory responses in the experimental autoimmune encephalomyelitis model of multiple sclerosis. Since hepatic macrophages are responsible for sepsis-induced liver injury, we investigated herein the capacity of transgenic SRG3 overexpression (SRG3 mice) to modulate sepsis in mice exposed to lipopolysaccharide (LPS) plus d-galactosamine (d-GalN). Our results demonstrated that ubiquitous SRG3 overexpression significantly protects mice from LPS/d-GalN-induced lethality mediated by hepatic M1 macrophages.
View Article and Find Full Text PDFInt J Mol Sci
February 2021
Department of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, Seoul 05006, Korea.
The SWItch (SWI)3-related gene (SRG3) product, a SWI/Sucrose Non-Fermenting (SNF) chromatin remodeling subunit, plays a critical role in regulating immune responses. We have previously shown that ubiquitous SRG3 overexpression attenuates the progression of Th1/Th17-mediated experimental autoimmune encephalomyelitis. However, it is unclear whether SRG3 overexpression can affect the pathogenesis of inflammatory skin diseases such as atopic dermatitis (AD), a Th2-type immune disorder.
View Article and Find Full Text PDFPLoS One
April 2016
Dept. of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul 143-747, Korea.
Although SWI3-related gene (SRG3), a chromatin remodeling factor, is critical for various biological processes including early embryogenesis and thymocyte development, it is unclear whether SRG3 is involved in the differentiation of CD4+ T cells, the key mediator of adaptive immune responses. Because it is known that experimental autoimmune encephalomyelitis (EAE) development is determined by the activation of CD4+ T helper cells, here, we investigated the role of SRG3 in EAE development using SRG3 transgenic mouse models exhibiting two distinct SRG3 expression patterns: SRG3 expression driven by either the CD2 or β-actin promoter. We found that the outcome of EAE development was completely different depending on the expression pattern of SRG3.
View Article and Find Full Text PDFJ Biol Chem
May 2008
Department of Biological Sciences, Institute of Molecular Biology and Genetics, Research Center for Functional Cellulomics, Seoul National University, Seoul 151-742, Korea.
To understand the tumor-suppressing mechanism of the SWI/SNF chromatin remodeling complex, we investigated its molecular relationship with p53. Using the pREP4-luc episomal reporter, we first demonstrated that p53 utilizes the chromatin remodeling activity of the SWI/SNF complex to initiate transcription from the chromatin-structured promoter. Among the components of the SWI/SNF complex, we identified BAF60a as a mediator of the interaction with p53 by the yeast two-hybrid assay.
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