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Updated: May 25, 2026

In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing
Published on: May 5, 2023
Kaiso uses all three zinc fingers and adjacent sequence motifs for high affinity binding to sequence-specific and
Bethany A Buck-Koehntop1, Maria A Martinez-Yamout, H Jane Dyson
1Department of Molecular Biology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Abstract:
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.
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