Reciprocal Id expression and myelin gene regulation in Schwann cells

Id proteins are thought to act as dominant negative antagonists of basic he lix-loop-helix (bHLH) transcription factors that direct differentiation in various cell types. We found that Schwann cells express all four Id-family genes and that their transcript levels were reciprocally regulated in pairs during nerve maturation in vivo and cAMP-mediated differentiation in vitro . The rapid induction as part of the early response to axonal membranes and cytokines suggested that Id3 is involved in myelin gene repression. An inv erse relationship between Id1/3 and myelin P0 expression was consistent wit h a role for these two Id proteins as inhibitors of differentiation, and Id 1/3 proteins strongly repressed myelin gene promoter activity. Nuclear fact ors isolated from Schwann cells and intact sciatic nerves were found to bin d three different HLH recognition sequences (E boxes) in the proximal regio n of the P0 promoter, and production of these DNA binding complexes was alt ered during differentiation. These data support the concept that Id protein s regulate myelin gene expression by controlling the formation of specific bHLH DNA binding complexes with different E-box preferences.