Tissue Specificity and Cell Death are Associated with Specific Alterations in Nuclear Matrix Proteins

Abstract

The ability of identical signals to interact with specific tissues in the same animal and result in the expression of different genes, is a fundamental question in cell regulation. A suitable model system for investigating the tissue specific regulation of gene expression is found in comparing the dihydrotestosteone (DHT) response in ventral prostate with the seminal vesicle. The rat ventral prostate and the seminal vesicle both contain the same genome, posses nuclear DHT receptors, and respond to DHT with the production of markedly different secretory products (figure 1). Upon DHT stimulation, the ventral prostate produces several specific secretory proteins. Similarly, the seminal vesicle produces its own unique tissue specific secretory proteins (figure 2). These tissue specific secretory proteins are all under control of the androgen receptor. Evidently there is another formes) of regulation which determines what genes are activated when the cells are stimulated with androgen. We hypothesize that this regulation is brought about by alterations in the three dimensional conformation of the genome within the nucleus. It is believed that the genomic configuration within the nucleus is determined in part by the binding of DNA loop domains to the nuclear matrix proteins. If the ventral prostate and seminal vesicle each possess unique conformations of their DNA, it is possible that the androgen receptor is able to bind and activate tissue specific transcription on different locations of the DNA depending on the tissue. Since the nuclear matrix is the organizing structure of the DNA in the nucleus, tissue specificity in three dimensional DNA organization may be caused by a unique nuclear matrix composition. We propose that the nuclear matrix is tissue specific and is involved in the regulation of gene expression.