BASIC HELIX-LOOP-HELIX PROTEIN SEQUENCES DETERMINING DIFFERENTIAL INHIBITION BY CALMODULIN AND S-100 PROTEINS

Basic helix-loop-helix (bHLH) proteins are a group of transcription fa ctors that are involved in differentiation and numerous other cellular processes. The proteins include the widely expressed class A bHLH pro teins (E proteins) and the tissue specific class E proteins. Previous studies have shown that calmodulin can inhibit the DNA binding activit y of certain E proteins but not their heterodimers with class B protei ns. Here we show that calmodulin binds to the DNA-interacting basic se quence within the bHLH domain of E proteins. The strength of the bindi ng of bHLH proteins to calmodulin correlates directly with the calmodu lin sensitivity of their DNA binding, The basic sequence of MyoD, a cl ass B protein, can also interact with calmodulin. This interaction, ho wever, is blocked by MyoD sequences directly N-terminal of the basic s equence. We further demonstrate that S-100 proteins can interact with and differentially inhibit the DNA binding of bHLH proteins through in teraction with the basic sequence, Both the binding to the basic seque nce and the effect of the directly N-terminal sequence vary for differ ent 5-100 proteins and bHLH proteins, The results suggest the involvem ent of both calmodulin and S-100 proteins in the differential regulati on of bHLH proteins.