An atypical homeodomain in SATB1 promotes specific recognition of the key structural element in a matrix attachment region.
SATB1 is a cell type-specific nuclear matrix attachment region (MAR) DNA-binding protein, predominantly expressed in thymocytes. We identified an atypical homeodomain and two Cut-like repeats in SATB1, in addition to the known MAR-binding domain. The isolated MAR-binding domain recognizes a certain DNA sequence context within MARs that is highly potentiated for base unpairing. Unlike the MAR-binding domain, the homeodomain when isolated binds poorly and with low specificity to DNA. However, the combined action of the MAR-binding domain and the homeodomain allows SATB1 to specifically recognize the core unwinding element within the base-unpairing region. The core unwinding element is critical for MAR structure, since point mutations within this core abolish the unwinding propensity of the MAR. The contribution of the homeodomain is abolished by alanine substitutions of arginine 3 and arginine 5 in the N-terminal arm of the homeodomain. Site-directed mutagenesis of the core unwinding element in the 3' MAR of the immunoglobulin heavy chain gene enhancer revealed the sequence 5'-(C/A)TAATA-3' to be essential for the increase in affinity mediated by the homeodomain. SATB1 may regulate T-cell development and function at the level of higher order chromatin structure through the critical DNA structural elements within MARs.
Dickinson
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Burnham Institute, La Jolla Cancer Research Center, La Jolla, California 92037, USA.
Dickinson
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Kohwi-Shigematsu
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D000595:Amino Acid Sequence; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D036961:Matrix Attachment Region Binding Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D015530:Nuclear Matrix / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics; D011485:Protein Binding; D011487:Protein Conformation; D012097:Repressor Proteins / Q000235:genetics; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors
C080632:CUX1 protein, human; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D036961:Matrix Attachment Region Binding Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C076189:SATB1 protein, human; D014157:Transcription Factors; D004247:DNA