title: Human CD1D gene expression is regulated by LEF-1 through distal promoter regulatory elements.
abstract: CD1d-expressing cells present lipid Ag to CD1d-restricted NKT cells, which play an important role in immune regulation and tumor rejection. Lymphoid enhancer-binding factor-1 (LEF-1) is one of the regulators of the Wnt signaling pathway, which is a powerful regulator in cellular growth, differentiation, and transformation. There is little evidence connecting Wnt signaling to CD1d expression. In this study, we have identified LEF-1 as a regulator of the expression of the gene encoding the human CD1d molecule (CD1D). We found that LEF-1 binds specifically to the CD1D promoter. Overexpression of LEF-1 in K562 or Jurkat cells suppresses CD1D promoter activity and downregulates endogenous CD1D transcripts, whereas knockdown of LEF-1 using LEF-1-specific small interfering RNA increases CD1D transcripts in K562 and Jurkat cells but there are different levels of surface CD1d on these two cell types. Chromatin immunoprecipitation showed that the endogenous LEF-1 is situated at the CD1D promoter and interacts with histone deacetylase-1 to facilitate the transcriptional repressor activity. Knockdown of LEF-1 using small interfering RNA potentiates an acetylation state of histone H3/H4, supporting the notion that LEF-1 acts as a transcriptional repressor for the CD1D gene. Our finding links LEF-1 to CD1D and suggests a role of Wnt signaling in the regulation of the human CD1D gene.
authors.affiliation: Qugene Corporation, Metairie, LA 70003, USA. qchen@qugene.com
authors.forename: Qiao-Yi
authors.initials: QY
authors.lastname: Chen
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Seth H
authors.initials: SH
authors.lastname: Pincus
authors.forename: Shixiu
authors.initials: S
authors.lastname: Wu
authors.forename: David
authors.initials: D
authors.lastname: Ricks
authors.forename: Donald
authors.initials: D
authors.lastname: Liu
authors.forename: Zhongsheng
authors.initials: Z
authors.lastname: Sun
authors.forename: Noel
authors.initials: N
authors.lastname: Maclaren
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lan
mesh_terms: D055610:Antigens, CD1d / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D055785:Gene Knockdown Techniques; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000276:immunology*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D051153:Wnt Proteins / Q000502:physiology
chemical_list: D055610:Antigens, CD1d; C526877:CD1D protein, human; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D051153:Wnt Proteins