Structural basis for recognition of the matrix attachment region of DNA by transcription factor SATB1

• Published in: Nucleic acids research Vol. 35; no. 15; pp. 5073 - 5084
• Main Authors: Yamasaki, Kazuhiko, Akiba, Toshihiko, Yamasaki, Tomoko, Harata, Kazuaki
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.08.2007; Oxford Publishing Limited (England)
• Subjects: Amino Acid Sequence; Binding Sites; Crystallography, X-Ray; DNA - chemistry; Evolution, Molecular; Matrix Attachment Region Binding Proteins - chemistry; Matrix Attachment Region Binding Proteins - genetics; Matrix Attachment Regions; Models, Molecular; Molecular Sequence Data; Mutation; Protein Structure, Tertiary; Sequence Homology; Structural Biology; Transcription Factors - chemistry; Transcription Factors - genetics
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkm504

Special AT-rich sequence binding protein 1 (SATB1) regulates gene expression essential in immune T-cell maturation and switching of fetal globin species, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin remodeling. Previously we have revealed a five-helix structure of the N-terminal CUT domain, which is essentially the folded region in the MAR-binding domain, of human SATB1 by NMR. Here we determined crystal structure of the complex of the CUT domain and a MAR DNA, in which the third helix of the CUT domain deeply enters the major groove of DNA in the B-form. Bases of 5′-CTAATA-3′ sequence are contacted by this helix, through direct and water-mediated hydrogen bonds and apolar and van der Waals contacts. Mutations at conserved base-contacting residues, Gln402 and Gly403, reduced the DNA-binding activity, which confirmed the importance of the observed interactions involving these residues. A significant number of equivalent contacts are observed also for typically four-helix POU-specific domains of POU-homologous proteins, indicating that these domains share a common framework of the DNA-binding mode, recognizing partially similar DNA sequences.