Silent and expressed sister Mup genes are located within distinct chromatin domains: analysis by pulsed-field gel electrophoresis and polymerase chain reaction-supplemented DNase I digestion.

We have recently described a subfamily of two genes, Mup-1.5a and Mup-1.5b, which exist as a nonallelic pair in most inbred strains of mice. The Mup-1.5a and Mup-1.5b genes are more than 99.9% homologous, yet they are differentially expressed. While the Mup-1.5a gene is expressed at a high level in the submaxillary gland, the Mup-1.5b gene does not appear to be expressed either in this or in any other tissue. The Mup-1.5b gene can, however, be expressed as a transgene with the tissue specificity of its sister gene, Mup-1.5a. We have shown before that both the Mup-1.5a and Mup-1.5b genes are located on chromosome 4, closely linked to the Mup-1 locus. In this report, we demonstrate the two genes are located within distinct chromosomal domains, separated by at least 150 to 200 kb of DNA. Using a novel method, detailed in this report, we show that in the submaxillary gland, the Mup-1.5a gene is five- to sixfold more susceptible to DNase I digestion than is the Mup-1.5b gene. This finding suggests that the inactivity of the Mup-1.5b gene is brought about by long range-acting mechanisms that establish a chromatin structure in the vicinity of this gene incompatible with transcription.