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

John J. Love, Xiang Li, David A. Case, Klaus Giese, Rudolf Crosschedl, Peter E. Wright

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)791-795
Number of pages5
JournalNature
Volume376
Issue number6543
DOIs
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • General

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    Love, J. J., Li, X., Case, D. A., Giese, K., Crosschedl, R., & Wright, P. E. (1995). Structural basis for DNA bending by the architectural transcription factor LEF-1. Nature, 376(6543), 791-795. https://doi.org/10.1038/376791a0