Cell structure and DNA organization.
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Biomedical subjects
R H Getzenberg
Publications and source records attributed to R H Getzenberg.
The tissue matrix: cell dynamics and hormone action.
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Tissue specificity of the hormonal response in sex accessory tissues is associated with nuclear matrix protein patterns.
The DNA of interphase nuclei have very specific three-dimensional organizations that are different in different cell types, and it is possible that this varying DNA organization is responsible for the tissue specificity of gene expression. The nuclear matrix organizes the three-dimensional structure of the DNA and is believed to be involved in the control of gene expression. This study compares the nuclear structural proteins between two sex accessory tissues in the same animal responding to the same androgen stimulation by the differential expression of major tissue-specific secretory proteins. We demonstrate here that the nuclear matrix is tissue specific in the rat ventral prostate and seminal vesicle, and undergoes characteristic alterations in its protein composition upon androgen withdrawal. Three types of nuclear matrix proteins were observed: 1) nuclear matrix proteins that are different and tissue specific in the rat ventral prostate and seminal vesicle, 2) a set of nuclear matrix proteins that either appear or disappear upon androgen withdrawal, and 3) a set of proteins that are common to both the ventral prostate and seminal vesicle and do not change with the hormonal state of the animal. Since the nuclear matrix is known to bind androgen receptors in a tissue- and steroid-specific manner, we propose that the tissue specificity of the nuclear matrix arranges the DNA in a unique conformation, which may be involved in the specific interaction of transcription factors with DNA sequences, resulting in tissue-specific patterns of secretory protein expression.
Androgen-Binding Protein↗
Rat seminal-vesicle secretory protein SVS II binds DNA with a preference for the 5' regulatory region of secretory protein SVS IV gene: co-isolation with components of the nuclear matrix.
In rats, the ventral prostate and seminal vesicles produce distinct sets of proteins whose functions and tissue-specific regulation by androgens remain unclear. We have utilized the genes encoding the major secretory protein of seminal vesicles, SVS IV, and the C3 subunit of prostatein of the ventral prostate to study how the nuclear matrix might determine their tissue-specific gene expression. Nuclear matrix proteins were prepared from purified nuclei with DNase and 2 M NaCl, separated in SDS gels, and transferred onto membranes for DNA-binding (southwestern) and immunological (western) analyses. The 5' region of the SVS IV gene (SVS IV-7S) bound to a 45,000-kDa molecular-weight protein band in the nuclear matrix of seminal vesicles but not to that of ventral prostate, kidney, or liver. Sequencing revealed that this band was a seminal-vesicle secretory protein, SVS II, whose identity was confirmed with an anti-SVS II antiserum in western blots. Actin-like protein, similar in mobility to SVS II, was detected in seminal-vesicle and ventral prostate nuclear matrix, but not in seminal-vesicle fluid. Reducing agent (10 mM dithiothreitol) and acidic (pH 6.5) buffer did not eliminate SVS II, but isolation of nuclear matrices with ammonium sulfate, nucleases, and urea decreased SVS II immunoreactivity and removed actin-like protein. SVS II binding to SVS IV-7S DNA was greater than its binding to either a comparable fragment of the C3 gene or linearized pUC-19 plasmid, and it was not eliminated by a 100-fold competition. When seminal-vesicle fluid was mixed with rat liver, some SVS II co-isolated with the nuclear-matrix proteins, indicating that nonspecific interactions contribute to its association with the nucleoskeleton. However, these interactions may not represent the intracellular behavior of SVS II in seminal-vesicle epithelium. Sequence comparisons indicate significant homologies between SVS II and some other seminal proteins, including bovine caltrin, which, under the name seminalplasmin, is known to possess antimicrobial activity. Collectively, these data suggest that in addition to its known functions, SVS II may also bind extraneous DNA in seminal fluid. Additionally, SVS II may participate as a structural component in the organization of a tissue-specific seminal-vesicle nuclear matrix.
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