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

Abstract

AbstractWe 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.