Human Interleukin-9: Genomic Sequence, Chromosomal Location, and Sequences Essential for Its Expression in Human T-Cell Leukemia Virus (HTLV)-I-Transformed Human T Cells

• Published in: Blood 1991-04, Vol.77 (7), p.1436-1441
• Main Authors: Kelleher, Kerry, Bean, Kevin, Clark, Steven C., Leung, Wah-Ying, Yang-Feng, Teresa L., Chen, Janice W., Lin, Pin-Fang, Luo, Wen, Yang, Yu-Chung
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Base Sequence; Biological and medical sciences; Blotting, Southern; Cell Line; Cell Transformation, Viral; Chromosome Banding; Chromosomes, Human, Pair 5; Cloning, Molecular; DNA - genetics; DNA - isolation & purification; Genomic Library; Glycoproteins - genetics; Human T-lymphotropic virus 1 - genetics; Humans; Immunopathology; Interleukin-9; Interleukins - genetics; Medical sciences; Molecular Sequence Data; Promoter Regions, Genetic; Regulatory Sequences, Nucleic Acid; Restriction Mapping; Sequence Homology, Nucleic Acid; T-Lymphocytes - immunology; Transcription, Genetic
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V77.7.1436.1436

We have isolated the genomic sequence of human interleukin-9 (IL-9) based on its sequence homology with a human IL-9 cDNA isolated from human T-cell leukemia virus (HTLV)-l-transformed T cells by expression cloning. The entire genomic sequence has been determined and the gene consists of five exons and four introns. The human IL-9 gene is mapped to the long arm of human chromosome 5 at band 5q31-32, a region found to be deleted in a number of patients with acquired 5q– abnormalities and hematologic disorders. Several blocks of transcriptional control sequences have been identified at the 5'-flanking region of the human IL-9 gene that may play an important role in the control of IL-9 gene expression. The 5'-regulatory region of the human IL-9 gene also contains sequences identified in the 5'-flanking regions of other cytokine genes mapped to the long arm of human chromosome 5, including IL-3, IL-4, IL-5, and granulocyte-macrophage colony-stimulating factor and other T-cell growth factor genes including IL-2 and IL-6. The IL-9 gene is constitutively expressed in the HTLV-l-transformed human T cells and the expression of IL-9 in these cells can be further induced by 12-O-tetradecanoyl phorbol 13-acetate. Transient transfection analysis using the plasmid containing the 5-flanking region of IL-9 gene upstream from the firefly lu-ciferase reporter gene indicated that the 0.9-kb Sma\-Sac\ fragment of the IL-9 gene contains sequences required for the constitutive and activated expression of IL-9 gene in HTLV-l-transformed cells. These results will now allow us to study the regulatory mechanisms of IL-9 gene expression in normal and leukemic human T cells.