Predictive base substitution rules that determine the binding and transcriptional specificity of Maf recognition elements.
Small Maf transcription factors possess a basic region-leucine zipper motif through which they form homodimers or heterodimers with CNC and Bach proteins. Different combinations of small Maf and CNC/Bach protein dimers bind to cis-acting DNA elements, collectively referred to as Maf-recognition elements (MAREs), to either activate or repress transcription. As MAREs defined by function are often divergent from the consensus sequence, we speculated that sequence variations in the MAREs form the basis for selective Maf:Maf or Maf:CNC dimer binding. To test this hypothesis, we analyzed the binding of Maf-containing dimers to variant sequences of the MARE using bacterially expressed MafG and Nrf2 proteins and a surface plasmon resonance-microarray imaging technique. We found that base substitutions in the MAREs actually determined their binding preference for different dimers. In fact, we were able to categorize MAREs into five groups: MafG homodimer-orientd MAREs (Groups I and II), ambivalent MAREs (Group III), MafG:Nrf2 heterodimer-orientd MAREs (Group IV), and silent MAREs (Group V). This study thus manifests that a clear set of rules pertaining to the cis-acting element determine whether a given MARE preferentially associates with MafG homodimer or with MafG:Nrf2 heterodimer.
Yamamoto
Tae
T
Graduate School of Comprehensive Human Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577, Japan.
Kyo
Motoki
M
Kamiya
Terue
T
Tanaka
Toshiyuki
T
Engel
James Douglas
JD
Motohashi
Hozumi
H
Yamamoto
Masayuki
M
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D017124:Conserved Sequence; D019281:Dimerization; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D007700:Kinetics; D051259:MafG Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D020218:Response Elements; D020349:Surface Plasmon Resonance; D014158:Transcription, Genetic
C103944:MAFG protein, human; D051259:MafG Transcription Factor; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D012097:Repressor Proteins