Octamer transcription factors 1 and 2 each bind to two different functional elements in the immunoglobulin heavy-chain promoter

Abstract

Immunoglobulin heavy-chain genes contain two conserved sequence elements 5' to the site of transcription initiation: the octamer ATGCAAAT and the heptamer CTCATGA. Both of these elements are required for normal cell-specific promoter function. The present study demonstrates that both the ubiquitous and lymphoid-cell-specific octamer transcription factors (OTF-1 and OTF-2, respectively) interact specifically with each of the two conserved sequence elements, forming either homo- or heterodimeric complexes. This was surprising, since the heptamer and octamer sequence motifs bear no obvious similarity to each other. Binding of either factor to the octamer element occurred independently. However, OTF interaction with the heptamer sequence appeared to require the presence of an intact octamer motif and occurred with a spacing of either 2 or 14 base pairs between the two elements, suggesting coordinate binding resulting from protein-protein interactions. The degeneracy in sequences recognized by the OTFs may be important in widening the range over which gene expression can be modulated and in establishing cell type specificity.