Regulation of polypeptide-hormone biosynthesis at the level of the genome

Abstract

Understanding of gene control mechanisms has greatly accelerated largely due to the application of recombinant DNA techniques. Polypeptide hormone genes encode multiexonic-intronic transcriptional sequences, the exons of which in turn encode polyprotein precursors or prohormones from which the hormones are cleaved during posttranslational processing of the prohormones. Transcriptional processes are regulated by at least two qualitatively different modes of gene regulation. The first mode includes the factors and structural components of a gene that determine whether a gene can or cannot be expressed in a given tissue when the appropriate inducer is present. The second mode is the physiological induction and regulation of the gene that can normally be expressed in a particular tissue. Both cis and trans regulatory mechanisms appear to operate in both tissue-specific expression and physiological regulation. Tissue-specific enhancer sequences consisting of short nucleotide sequences of from 10 to 50 base pairs have been identified in or around genes that are expressed in specific tissues. In many instances trans-acting DNA binding proteins have been found to repress or activate the transcription of the genes. Physiological regulation of hormone genes involves at least two different classes of macromolecules, steroid hormone receptors and phosphoproteins that are formed in response to the binding of ligands to specific surface-located receptors. Although the precise mechanisms by which information encoded in cellular effectors is coupled to cellular responses is incomplete, continued investigations should lead to a more complete understanding of gene control mechanisms and the eventual ability to alter the expression of specific genes.