Human CD1D gene has TATA boxless dual promoters: an SP1-binding element determines the function of the proximal promoter.
CD1d presents lipid Ags to a specific population of NK T cells, which are involved in the host immune defense, suppression of autoimmunity, and the rejection of tumor cells. The transcriptional control mechanism that determines the regulation and the tissue distribution of CD1d remains largely unknown. After investigating 3.7 kb 5' upstream of the coding region, we found that human gene encoding CD1d molecule (CD1D) has TATA boxless dual promoters with multiple transcription initiation sites. The proximal promoter is located within the region of -106 to +24, and the distal promoter is located within the region of -665 to -202 with the A of the translational start codon defined as +1. The longest 5'-untranslated region derived from 5'-RACE and apparently generated by the distal promoter has 272 bp in length covering the genomic sequence of the proximal promoter. The region covering the proximal promoter gave a much higher luciferase activity in Jurkat cells than in K562 cells, whereas it was in reverse for the region covering the distal promoter, indicating a cell type sp. act. of the two promoters. Transcription factor SP1 plays a crucial role in the function of the proximal promoter. The analysis of the CD1D promoter region indicates that IFN-gamma, NF-IL-6, and T cell factor 1/lymphoid enhancer-binding factor 1 are most likely involved in the regulation of CD1d expression. The illustration of the dual CD1D gene promoters will help to reveal the regulatory factors that control CD1d expression and its tissue distribution for a better understanding of the cross-regulation between CD1d and NK T cells.
Chen
Qiao-Yi
QY
Research Institute for Children, Children's Hospital, New Orleans, LA 70118, USA. qchen@chnola-research.org
Jackson
Natalie
N
D024506:5' Flanking Region / Q000276:immunology; D020121:5' Untranslated Regions / Q000276:immunology; D018949:Antigens, CD1 / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D055610:Antigens, CD1d; D001483:Base Sequence; D003001:Cloning, Molecular; D005822:Genetic Vectors; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic / Q000276:immunology*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D012045:Regulatory Sequences, Nucleic Acid / Q000276:immunology*; D020218:Response Elements / Q000276:immunology; D017422:Sequence Analysis, DNA; D016329:Sp1 Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D016385:TATA Box / Q000276:immunology*
D020121:5' Untranslated Regions; D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D016329:Sp1 Transcription Factor