2 - The regulation of insulin gene expression

Summary

Summary

Insulin biosynthesis in adult vertebrates is strictly confined to the B-cells of the endocrine pancreas. The molecular mechanisms underlying this selective expression of the insulin gene, and of other genes whose expression is also regulated in cell-specific fashion, are beginning to be revealed, largely through the application of recombinant DNA and gene transfer methodologies. A critical point of control in insulin gene expression is at the stage of transcription initiation. The effects are mediated through specific DNA sequences located in the 5′-flanking region of the gene, and appear to involve recognition of these sequences by protein factors present in B-cells. The characterization of such sequence-specific DNA binding proteins and the genes which encode them will contribute decisively to our understanding of differentiation and development of the endocrine pancreas.

Introduction

As a multicellular organism develops, dramatic morphological differences appear among the various cell types, culminating in the generation of the final differentiated phenotype. These changes are associated with, and to a large extent caused by, alterations in gene expression. Thus a molecular understanding of development requires the elucidation of the process of selective gene expression, both at the level of the final differentiated cell and at earlier stages of development where a commitment (or determination) to differentiate has occurred but no morphological changes are yet apparent. In general, the process of differentiation is not accompanied by extensive loss or rearrangement of the genetic material (Gurdon, 1974). Indeed, under appropriate experimental circumstances, the differentiated cell exhibits considerable ‘plasticity’ or ability to express genes characteristic of an alternative cell type, for example following cell fusion (Blau et al., 1985).