Hox Transcription Factors Access the RNA Polymerase II Machinery through Direct Homeodomain Binding to a Conserved Motif of Mediator Subunit Med19

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Mutations of Hox developmental genes in the fruit fly Drosophila melanogaster may provoke spectacular changes in form: transformations of one body part into another, or loss of organs. This attribute identifies them as important developmental genes. Insect and vertebrate Hox proteins contain highly related homeodomain motifs used to bind to regulatory DNA and influence expression of developmental target genes. This occurs at the level of transcription of target gene DNA to messenger RNA by RNA polymerase II and its associated protein machinery (>50 proteins). How Hox homeodomain proteins induce fine-tuned transcription remains an open question. We provide an initial response, finding that Hox proteins also use their homeodomains to bind one machinery protein, Mediator complex subunit 19 (Med19) through a Med19 sequence that is highly conserved in animal phyla. Med19 mutants isolated in this work (the first animal mutants) show that Med19 assists Hox protein functions. Further, they indicate that homeodomain binding to the Med19 motif is required for normal expression of a Hox target gene. Our work provides new clues for understanding how the specific transcriptional inputs of the highly conserved Hox class of transcription factors are integrated at the level of the whole transcription machinery.

Vyšlo v časopise: Hox Transcription Factors Access the RNA Polymerase II Machinery through Direct Homeodomain Binding to a Conserved Motif of Mediator Subunit Med19. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004303
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004303

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