A new transcriptional-activation motif restricted to a class of helix-loop-helix proteins is functionally conserved in both yeast and mammalian cells.
Previous studies demonstrated that the amino-terminal portions of E2A and E2-2 are crucial for transactivation. Subsequent findings showed that the same amino-terminal region of E2A is involved in two different translocation events contributing to the induction of a pre-B-cell acute lymphoblastic leukemia and a pro-B-cell acute lymphoblastic leukemia. These results led us to focus on the amino-terminal region of E2A to better understand its normal role in transcriptional regulation and its aberrant involvement in the two leukemias. We report here the identification of two conserved boxes in the E2A amino-terminal domain that show extensive homology within the transactivation domains of E12, E47, E2-2, HEB, and daughterless, all members of the same class of helix-loop-helix proteins. Together, both boxes are crucial for transcriptional activation and have the potential to form a new activation motif, that of a loop adjacent to an amphipathic alpha-helix, designated the loop-helix (LH) motif. A minimal region containing the LH motif is sufficient for transcriptional activation. Point mutations in the amphipathic helix of the minimal region reduce its transactivation capabilities dramatically. The same constructs expressed in yeast cells show identical patterns of activation, suggesting that the LH motif and its target proteins are functionally conserved in yeast cells. We propose that the LH motif represents a novel transactivation domain that is distinct from the previously characterized acidic blob, proline-rich, and glutamine-rich activation motifs. In addition, the LH motif is the first activation motif restricted to one class of DNA binding proteins.
Quong
M W
MW
Department of Biology, University of California, San Diego, La Jolla 92093.
Massari
M E
ME
Zwart
R
R
Murre
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017124:Conserved Sequence; D004247:DNA; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000235:genetics; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015003:Yeasts / Q000235:genetics
D004268:DNA-Binding Proteins; D051820:TCF Transcription Factors; C544912:TCF7L1 protein, human; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D004247:DNA