A genome-scale analysis of the cis-regulatory circuitry underlying sonic hedgehog-mediated patterning of the mammalian limb Export

@article{vokes_genome-scale_2008, abstract = {Sonic hedgehog (Shh) signals via Gli transcription factors to direct digit number and identity in the vertebrate limb. We characterized the Gli-dependent cis-regulatory network through a combination of whole-genome chromatin immunoprecipitation (ChIP)-on-chip and transcriptional profiling of the developing mouse limb. These analyses identified [{\\textasciitilde}]5000 high-quality Gli3-binding sites, including all known Gli-dependent enhancers. Discrete binding regions exhibit a higher-order clustering, highlighting the complexity of cis-regulatory interactions. Further, Gli3 binds inertly to previously identified neural-specific Gli enhancers, demonstrating the accessibility of their cis-regulatory elements. Intersection of DNA binding data with gene expression profiles predicted 205 putative limb target genes. A subset of putative cis-regulatory regions were analyzed in transgenic embryos, establishing Blimp1 as a direct Gli target and identifying Gli activator signaling in a direct, long-range regulation of the BMP antagonist Gremlin. In contrast, a long-range silencer cassette downstream from Hand2 likely mediates Gli3 repression in the anterior limb. These studies provide the first comprehensive characterization of the transcriptional output of a Shh-patterning process in the mammalian embryo and a framework for elaborating regulatory networks in the developing limb.}, author = {Vokes, Steven A. and Ji, Hongkai and Wong, Wing H. and Mcmahon, Andrew P.}, citeulike-article-id = {3366714}, citeulike-linkout-0 = {http://dx.doi.org/10.1101/gad.1693008}, citeulike-linkout-1 = {http://genesdev.cshlp.org/cgi/content/abstract/22/19/2651}, doi = {10.1101/gad.1693008}, journal = {Genes Dev.}, keywords = {chip, genome}, month = {October}, number = {19}, pages = {2651--2663}, posted-at = {2008-10-02 16:03:26}, priority = {2}, title = {A genome-scale analysis of the cis-regulatory circuitry underlying sonic hedgehog-mediated patterning of the mammalian limb}, url = {http://dx.doi.org/10.1101/gad.1693008}, volume = {22}, year = {2008} }

TY - JOUR ID - vokes_genome-scale_2008 L3 - citeulike-article-id:3366714 N2 - Sonic hedgehog (Shh) signals via Gli transcription factors to direct digit number and identity in the vertebrate limb. We characterized the Gli-dependent cis-regulatory network through a combination of whole-genome chromatin immunoprecipitation (ChIP)-on-chip and transcriptional profiling of the developing mouse limb. These analyses identified [{\\textasciitilde}]5000 high-quality Gli3-binding sites, including all known Gli-dependent enhancers. Discrete binding regions exhibit a higher-order clustering, highlighting the complexity of cis-regulatory interactions. Further, Gli3 binds inertly to previously identified neural-specific Gli enhancers, demonstrating the accessibility of their cis-regulatory elements. Intersection of DNA binding data with gene expression profiles predicted 205 putative limb target genes. A subset of putative cis-regulatory regions were analyzed in transgenic embryos, establishing Blimp1 as a direct Gli target and identifying Gli activator signaling in a direct, long-range regulation of the BMP antagonist Gremlin. In contrast, a long-range silencer cassette downstream from Hand2 likely mediates Gli3 repression in the anterior limb. These studies provide the first comprehensive characterization of the transcriptional output of a Shh-patterning process in the mammalian embryo and a framework for elaborating regulatory networks in the developing limb. IS - 19 JF - Genes Dev. EP - 2663 TI - A genome-scale analysis of the cis-regulatory circuitry underlying sonic hedgehog-mediated patterning of the mammalian limb VL - 22 SP - 2651 KW - chip KW - genome AU - Vokes, Steven AU - Ji, Hongkai AU - Wong, Wing AU - Mcmahon, Andrew PY - 2008/October// UR - http://dx.doi.org/10.1101/gad.1693008 ER -