TRANSFORMATION BY HOMEOBOX GENES CAN BE MEDIATED BY SELECTIVE TRANSCRIPTIONAL REPRESSION

Altered transcription is a recurrent theme in the field of cancer biol ogy. But despite the central role of transcription in transformation, little is known about the mechanism by which dominant nuclear oncogene s induce malignancies. Homeobox family proteins are prominent examples of transcriptional regulators which control development and can funct ion as oncogenes. Here we explore the molecular basis for transformati on by this class of regulators using Oct-2 and Oct-1. We show that the DNA binding POU domains of these proteins are selective and sequence- specific transcriptional repressors that produce malignant lymphomas w hen they are expressed in T cells of transgenic mice. Mutagenesis expe riments identified a specific set of promoters, those containing octam er regulatory elements, as the targets for transformation by selective inhibition of gene expression.