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Caudal-like PAL-1 directly activates the bodywall muscle module regulator hlh-1 in C. elegans to initiate the embryonic muscle gene regulatory network.

http://www.ncbi.nlm.nih.gov/pubmed/19261701

Previous work in C. elegans has shown that posterior embryonic bodywall muscle lineages are regulated through a genetically defined transcriptional cascade that includes PAL-1/Caudal-mediated activation of muscle-specific transcription factors, including HLH-1/MRF and UNC-120/SRF, which together orchestrate specification and differentiation. Using chromatin immunoprecipitation (ChIP) in embryos, we now demonstrate direct binding of PAL-1 in vivo to an hlh-1 enhancer element. Through mutational analysis of the evolutionarily conserved sequences within this enhancer, we identify two cis-acting elements and their associated transacting factors (PAL-1 and HLH-1) that are crucial for the temporal-spatial expression of hlh-1 and proper myogenesis. Our data demonstrate that hlh-1 is indeed a direct target of PAL-1 in the posterior embryonic C. elegans muscle lineages, defining a novel in vivo binding site for this crucial developmental regulator. We find that the same enhancer element is also a target of HLH-1 positive auto regulation, underlying (at least in part) the sustained high levels of CeMyoD in bodywall muscle throughout development. Together, these results provide a molecular framework for the gene regulatory network activating the muscle module during embryogenesis.

Pubmed ID: 19261701 RIS Download

Mesh terms: Animals | Base Sequence | Binding Sites | Caenorhabditis elegans | Caenorhabditis elegans Proteins | Conserved Sequence | Embryo, Nonmammalian | Evolution, Molecular | Gene Expression Regulation, Developmental | Gene Regulatory Networks | Homeodomain Proteins | Molecular Sequence Data | Muscles | Myogenic Regulatory Factors | Protein Binding | Sequence Alignment | Substrate Specificity | Trans-Activators | Transcriptional Activation

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Associated grants

  • Agency: NIGMS NIH HHS, Id: R01 GM037706
  • Agency: NIGMS NIH HHS, Id: R01-GM066953
  • Agency: NIGMS NIH HHS, Id: R01-GM37706
  • Agency: Intramural NIH HHS, Id: Z01 DK036131-02

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