Kaiso uses all three zinc fingers and adjacent sequence motifs for high affinity binding to sequence-specific and methyl-CpG DNA targets.
Kaiso is a Cys(2)His(2) zinc finger (ZF) protein that mediates methyl-CpG-dependent and sequence-specific transcriptional repression. As a first step towards elucidating the structural and molecular basis for recognition of these disparate DNA sequences, the minimal binding region of Kaiso was identified and optimal DNA sequences for high-affinity interactions were characterized. Contrary to previous findings, Kaiso requires all three zinc fingers plus adjacent protein regions for DNA recognition. An N-terminal extension contributes to structural stability, while an extended C-terminal region augments DNA binding. Complexes formed between the optimized Kaiso construct and both DNA sequences are suitable for future structural evaluation.
Department of Molecular Biology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Bethany A
BA
Buck-Koehntop
Maria A
MA
Martinez-Yamout
H Jane
HJ
Dyson
Peter E
PE
Wright
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018899:CpG Islands; D004247:DNA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D011485:Protein Binding; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers / Q000235:genetics*
D014157:Transcription Factors; C492254:ZBTB33 protein, human; D004247:DNA