title: The TFG-TEC oncoprotein induces transcriptional activation of the human β-enolase gene via chromatin modification of the promoter region.
abstract: Recurrent chromosome translocations are the hallmark of many human cancers. A proportion of human extraskeletal myxoid chondrosarcomas (EMCs) are associated with the characteristic chromosomal translocation t(3;9)(q11-12;q22), which results in the formation of a chimeric protein in which the N-terminal domain of the TRK-fused gene (TFG) is fused to the translocated in extraskeletal chondrosarcoma (TEC; also called CHN, CSMF, MINOR, NOR1, and NR4A3) gene. The oncogenic effect of this translocation may be due to the higher transactivation ability of the TFG-TEC chimeric protein; however, downstream target genes of TFG-TEC have not yet been identified. The results presented here, demonstrate that TFG-TEC activates the human β-enolase promoter. EMSAs, ChIP assays, and luciferase reporter assays revealed that TFG-TEC upregulates β-enolase transcription by binding to two NGFI-B response element motifs located upstream of the putative transcription start site. In addition, northern blot, quantitative real-time PCR, and Western blot analyses showed that overexpression of TFG-TEC up-regulated β-enolase mRNA and protein expression in cultured cell lines. Finally, ChIP analyses revealed that TFG-TEC controls the activity of the endogenous β-enolase promoter by promoting histone H3 acetylation. Overall, the results presented here indicate that TFG-TEC triggers a regulatory gene hierarchy implicated in cancer cell metabolism. This finding may aid the development of new therapeutic strategies for the treatment of human EMCs. © 2015 Wiley Periodicals, Inc.
authors: Laboratory of Molecular and Cellular Biology, Department of Life Science, Sogang University, Seoul, Korea.
authors: Ah-Young
authors: AY
authors: Kim
authors: Laboratory of Molecular and Cellular Biology, Department of Life Science, Sogang University, Seoul, Korea.
authors: Bobae
authors: B
authors: Lim
authors: Laboratory of Molecular and Cellular Biology, Department of Life Science, Sogang University, Seoul, Korea.
authors: JeeHyun
authors: J
authors: Choi
authors: Laboratory of Molecular and Cellular Biology, Department of Life Science, Sogang University, Seoul, Korea. jkim@sogang.ac.kr.
authors: Jungho
authors: J
authors: Kim
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000235:genetics* / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D018204:Neoplasms, Connective and Soft Tissue / Q000235:genetics* / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014178:Translocation, Genetic; D033921:Vesicular Transport Proteins
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D015514:Oncogene Proteins, Fusion; D010751:Phosphopyruvate Hydratase; D011506:Proteins; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; C490412:NR4A3 protein, human; C096163:TFG protein, human; D033921:Vesicular Transport Proteins
keywords: TFG-TEC; chromosomal translocation; fusion protein; human extraskeletal myxoid chondrosarcoma; human β-enolase gene; transcription activation