A conserved motif present in a class of helix-loop-helix proteins activates transcription by direct recruitment of the SAGA complex

The class I helix-loop-helix (HLH) proteins, which include E2A, HEB, and E2 -2, have been shown to be required for lineage-specific gene expression dur ing T and B lymphocyte development. Additionally, the E2A proteins function to regulate V(D)J recombination, possibly by allowing access of variable r egion segments to the recombination machinery. The mechanisms by which E2A regulates transcription and recombination, however, are largely unknown. He re, we identify a novel motif, LDFS, present in the vertebrate class I HLH proteins as well as in a yeast HLH protein that is essential for transactiv ation. We provide both genetic and biochemical evidence that the highly con served LDFS motif stimulates transcription by direct recruitment of the SAG A histone acetyltransferase complex.