SELECTIVE GENE EXPRESSION WITHIN HORMONALLY ACTIVATED MULTIGENE FAMILIES

Abstract

ABSTRACT Many hormonally regulated genes are members of small multigene families of 3–20 genes which are expressed in a highly tissue-specific manner. These include genes coding for chicken ovalbumin, Xenopus vitellogenin, rat α 2u -globulin and mouse α-amylase. Not all members of these multigene families are transcribed equally efficiently when a hormone activates specific genes. Particular emphasis will be placed in this report on the selective activation by estrogen of the vitellogenin multigene family in male Xenopus liver. The hormone induces de novo the transcription of at least 4 vitellogenin genes which can be distinguished, by virtue of a 20% divergence in coding sequence, into 2 groups (A and B) of two genes each. There may be additional vitellogenin sequences which are not transcribed. We have found, both in whole animals and in a cell culture system, that the A and B groups of vitellogenin genes are not simultaneously activated and that accumulation of individual mRNAs does not proceed at identical rates at the onset of primary stimulation in male Xenopus hepatocytes. During secondary hormonal stimulation in male or primary stimulation of female hepatocytes, all 4 vitellogenin genes were activated with identical kinetics and to the same extent. Differential hormonal effects on conformation (as judged by DNase I sensitivity) and transcription of individual vitellogenin genes, measured simultaneously in isolated nuclei, confirmed that the differential transcription of the A and B groups of vitellogenin genes were paralleled by a similar selective sensitization of these two groups of genes to DNase I. Selective expression or differential rates of transcription of individual hormonally activated genes within a multigene family poses new questions concerning the regulation of their expression and the sites of interaction between the genes and hormone receptors.