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First published online 4 March 2009
doi: 10.1242/dev.030668

Development 136, 1241-1249 (2009)
Published by The Company of Biologists 2009
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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

Haiyan Lei1, Jun Liu2, Tetsunari Fukushige1, Andrew Fire3 and Michael Krause1,*

1 National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
2 Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
3 Departments of Pathology and Genetics, Stanford School of Medicine, Stanford, CA 94305, USA.

* Author for correspondence (e-mail: mwkrause{at}helix.nih.gov)

Accepted 9 February 2009

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.

Key words: C. elegans, Myogenesis, Caudal, MyoD, Embryogenesis


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