32 The Helix-Loop-Helix Motif: Structure and Function

Abstract

OVERVIEW
A central class of transcriptional regulatory proteins are those with an apparent helix-loop-helix (HLH) dimerization motif abutting a DNA-binding basic region. The HLH region allows for homodimerization but, more importantly, various HLH proteins can interact to form heterodimers. The heterodimers appear to be major players in determining the expression of differentiated cellular functions in various differentiated cell types.

INTRODUCTION
Control of initiation of mRNA synthesis involves the interaction of DNA-binding proteins with each other and with specific DNA sequence elements. Families of such DNA-binding proteins have been identified that are structurally related. Among these families are proteins containing a zinc finger domain, a POU/homeobox domain, and leucine zipper dimerization domains. We have recently identified a new family of proteins that have in common a conserved DNA-binding and dimerization domain, designated the HLH motif. The size of the known HLH family is large (>30 members) and growing. Protein-protein interactions can occur between various HLH members, forming hetero-oligomers. The formation of hetero-oligomers and the large size of the HLH protein family offer an enormous scope of complexity and regulation. The purpose of this chapter is to survey HLH proteins and discuss their role in development.

E-BOX REGULATORY ELEMENTS
A wide variety of regulatory elements have been identified in the past decade that are involved in the control of tissue- and developmental-specific gene expression. One class of such elements, the E boxes, are interesting because they seem to be involved in the control of transcription of a number of genes, expressed in...