The HMG domain of lymphoid enhancer factor 1 bends DNA and facilitates assembly of functional nucleoprotein structures

• Published in: Cell Vol. 69; no. 1; pp. 185 - 195
• Main Authors: Giese, Klaus, Cox, Jeffery, Grosschedl, Rudolf
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.04.1992
• Subjects: Base Sequence; Binding Sites - genetics; DNA - metabolism; DNA Nucleotidyltransferases - metabolism; DNA-Binding Proteins - metabolism; High Mobility Group Proteins - metabolism; Humans; Integrases; Lymphoid Enhancer-Binding Factor 1; Molecular Sequence Data; Nuclear Proteins - metabolism; Nucleic Acid Conformation; Nucleoproteins - metabolism; Recombination, Genetic - genetics; Sex-Determining Region Y Protein; Transcription Factors
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/0092-8674(92)90129-Z

The high mobility group (HMG) domain is a DNA-binding motif that is associated with several eukaryotic regulatory proteins, including the lymphoid enhancer-binding factor LEF-1 and the testis-determining factor SRY. Here, we provide evidence that DNA binding by the HMG domain of LEF-1 involves primarily minor groove contacts and induces a bend of approximately 130° in the DNA helix. Bending was also found to accompany sequence-specific DNA binding by the SRY-HMG domain. Examining possible regulatory roles of HMG domain-induced DNA bends, we found that LEF-1 can function in a manner similar to bacterial integration host factor and facilitate communication between widely separated protein-binding sites in a recombination assay. Together with the previous observation that LEF-1 by itself is unable to augment basal promoter activity, these data suggest that HMG domain proteins can serve as “architectural” elements in the assembly of higher-order nucleoprotein structures.