ID GENE-EXPRESSION DURING DEVELOPMENT AND MOLECULAR-CLONING OF THE HUMAN ID-1 GENE

Id genes encode helix-loop-helix proteins that inhibit transcription b y forming inactive heterodimers with basic helix-loop-helix (bHLH) pro teins. bHLH proteins normally form either homodimers or heterodimers w ith other bHLH proteins and bind to a DNA sequence element activating transcription. Id-containing heterodimers are inactive because Id prot eins lack the basic amino acid region necessary to form a DNA-binding domain. We have examined the relative levels of Id-1 and Id-2 mRNA dur ing normal development and in malignant tissues. In the course of thes e experiments we cloned and sequenced the human Id-1 cDNA. Two related cDNA molecules encoding human Id-1 mRNAs were identified. Id-1a is a cDNA of 958 nucleotides and can encode a protein of 135 amino acids. I d-1b cDNA is 1145 nucleotides, can encode a protein of 149 amino acids , and appears to be a splice variant of Id-1a. The amino acid sequence of human Id-1 is greater than 90% homologous to that of mouse Id-1. T he patterns of Id-1 and Id-2 expression during mouse development vary widely, and we detected Id-1 expression in human fetal and adult tissu es from lung, liver, and brain. High Id-1 mRNA expression was found in many human tumor cell lines, including those isolated from nervous sy stem tumors. We mapped Id-2 to human chromosome 2p25.