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 during T and B lymphocyte development. Additionally, the E2A proteins function to regulate V(D)J recombination, possibly by allowing access of variable region segments to the recombination machinery. The mechanisms by which E2A regulates transcription and recombination, however, are largely unknown. Here, 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 transactivation. We provide both genetic and biochemical evidence that the highly conserved LDFS motif stimulates transcription by direct recruitment of the SAGA histone acetyltransferase complex.
Massari
M E
ME
Department of Biology, University of California, San Diego, La Jolla 92093, USA.
Grant
P A
PA
Pray-Grant
M G
MG
Berger
S L
SL
Workman
J L
JL
Murre
C
C
D000595:Amino Acid Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D006367:HeLa Cells; D018257:Helix-Loop-Helix Motifs / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D051820:TCF Transcription Factors; D015534:Trans-Activators / Q000235:genetics; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics*; D014162:Transfection
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; C104438:RTG3 protein, S cerevisiae; C544894:TCF7L2 protein, human; C073366:TCF12 protein, human