AJP - Cell Physiology, Vol 249, Issue 3 191-C199, Copyright © 1985 by American Physiological Society
Regulation of polypeptide-hormone biosynthesis at the level of the genome
J. F. Habener
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.
