title: Synergistic induction of galectin-1 by CCAAT/enhancer binding protein alpha and hypoxia-inducible factor 1alpha and its role in differentiation of acute myeloid leukemic cells.
abstract: Galectin-1 is a member of the galectin family and has a high affinity for galactose and N-acetylglucosamine moieties of glycoproteins. It mediates multiple signal transduction pathways to modulate cellular proliferation, survival, differentiation, and migration. However, the mechanisms for the regulation of its expression remain greatly elusive. We reported previously that galectin-1 is a direct target of the hypoxia-inducible factor 1 (HIF-1), a key heterodimeric transcriptional factor for the cellular response to hypoxia. Here we show that CCAAT/enhancer binding protein α (C/EBPα), a critical transcriptional factor for hematopoietic cell differentiation, can directly activate galectin-1 through binding to the -48 to -42 bp region of its promoter. Based on the physical interaction of C/EBPα and HIF-1α, the synergistic transcriptional activity of C/EBPα and HIF-1α on the promoter of the galectin-1 gene is also found by chromatin immunoprecipitation (ChIP), ChIP followed by ChIP (ChIP-reChIP), and luciferase assay. Moreover, knockdown or chemical inhibition of galectin-1 partially blocks the differentiation induced by HIF-1α or C/EBPα, which can be rescued by recombinant galectin-1. These discoveries would shed new insights on the mechanisms for galectin-1 expression regulation and HIF-1α- and C/EBPα-induced leukemic cell differentiation.
authors: Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of the Ministry of Education of China and the Chemical Biology Division of Shanghai Universities E-Institutes, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Xu-Yun
authors: XY
authors: Zhao
authors: Ke-Wen
authors: KW
authors: Zhao
authors: Yi
authors: Y
authors: Jiang
authors: Meng
authors: M
authors: Zhao
authors: Guo-Qiang
authors: GQ
authors: Chen
mesh_terms: D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D037483:Galectin 1 / Q000096:biosynthesis* / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D055785:Gene Knockdown Techniques; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D020298:U937 Cells
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D037483:Galectin 1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C445499:LGALS1 protein, human; D009363:Neoplasm Proteins