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Development. 2009 Apr;136(8):1241-9. doi: 10.1242/dev.030668. Epub 2009 Mar 4.

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

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1
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Abstract

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.

PMID:
19261701
PMCID:
PMC2687460
DOI:
10.1242/dev.030668
[Indexed for MEDLINE]
Free PMC Article
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