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Structural basis for DNA bending by the architectural transcription factor LEF-1

Abstract

LYMPHOID enhancer-binding factor (LEF-1) and the closely related T-cell factor 1 (TCF-1) are sequence-specific and cell-type-specific DNA-binding proteins that play important regulatory roles in organogenesis and thymocyte differentiation1–5. LEF-1 participates in regulation of the enhancer associated with the T cell receptor (TCR)-α gene by inducing a sharp bend in the DNA and facilitating interactions between Ets-1, PEBP2-α, and ATF/ CREB transcription factors bound at sites flanking the LEF-1 site1,2,6,7. It seems that LEF-1 plays an architectural role in the assembly and function of this regulatory nucleoprotein complex7,8. LEF-1 recognizes a specific nucleotide sequence through a high-mobility-group (HMG) domain1,2. Proteins containing HMG domains bind DNA in the minor groove, bend the double helix6,9,10, and recognize four-way junctions and other irregular DNA structures9,11. Here we report the solution structure of a complex of the LEF-1 HMG domain and adjacent basic region with its cognate DNA. The structure reveals the HMG domain bound in the widened minor groove of a markedly distorted and bent double helix. The basic region binds across the narrowed major groove and contributes to DNA recognition.

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Love, J., Li, X., Case, D. et al. Structural basis for DNA bending by the architectural transcription factor LEF-1. Nature 376, 791–795 (1995). https://doi.org/10.1038/376791a0

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