Generating Context-Specific Functions with Intrinsically Disordered Domains

摘要: During animal development, Hox transcription factors specify many different tissues, including organs, appendages, and portions of structures that span the length animal, such as nervous system, musculature, ectoderm. Consequently, proteins must sense cellular identity respond by instigating appropriate gene regulatory program. To further complicate matters, interact with DNA via a homeodomain, which binds high affinity yet notoriously low specificity. Using Drosophila protein Ultrabithorax (Ubx) model we have discovered most Ubx sequences outside homeodomain are intrinsically disordered regulate binding. An region near modulates both This also mediates interactions co-factor Extradenticle, is alternatively spliced. Extradenticle availability alternative splicing may control site selection. genes in position-specific manner within single tissue. A second large domain required to bind controlled WNT TGFb/BMP cell signaling cascades. Since these pathways subdivide Ubx-specified structures, this mechanism regulation field. Finally, once has bound DNA, it select whether activate or repress transcription. We find binding induces conformational change, increases solvent exposure activation domain. currently investigating change allows sequence dictate mode regulation. our carefully developed methods generate assay soluble, full-length melanogaster Ubx, identifying mechanisms drive context-specific function response increasingly spatially restricted cues (tissue identity, location tissue, sequence).