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Status |
Public on Sep 15, 2008 |
Title |
A Genome-Scale Analysis of the Cis-Regulatory Circuitry Underlying Hedgehog Mediated Patterning of the Mammalian Limb |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Sonic hedgehog (Shh) signals via Gli transcription factors to direct digit number and identity in the vertebrate limb. We have characterized the Gli-dependent cis-regulatory network through a combination of whole genome ChIP-on-chip and transcriptional profiling of the developing mouse limb. These analyses identified approximately 5,000 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 of 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.
This SuperSeries is composed of the SubSeries listed below.
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Overall design |
Refer to individual Series
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Citation(s) |
18832070 |
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Submission date |
Apr 07, 2008 |
Last update date |
Jan 29, 2022 |
Contact name |
Steven A. Vokes |
E-mail(s) |
svokes@austin.utexas.edu
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Organization name |
University of Texas at Austin
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Department |
Molecular Biosciences
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Street address |
2500 Speedway, STOP A5000
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City |
Austin |
State/province |
Texas |
ZIP/Postal code |
78757 |
Country |
USA |
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Platforms (9)
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GPL5811 |
[Mm_PromPR] Affymetrix Mouse Promoter 1.0R Array |
GPL6096 |
[MoEx-1_0-st] Affymetrix Mouse Exon 1.0 ST Array [transcript (gene) version] |
GPL6444 |
[Mm35b_P01R] Affymetrix Mouse Tiling 2.0R Set, Array 1 |
GPL6445 |
[Mm35b_P02R] Affymetrix Mouse Tiling 2.0R Set, Array 2 |
GPL6446 |
[Mm35b_P03R] Affymetrix Mouse Tiling 2.0R Set, Array 3 |
GPL6447 |
[Mm35b_P04R] Affymetrix Mouse Tiling 2.0R Set, Array 4 |
GPL6448 |
[Mm35b_P05R] Affymetrix Mouse Tiling 2.0R Set, Array 5 |
GPL6449 |
[Mm35b_P06R] Affymetrix Mouse Tiling 2.0R Set, Array 6 |
GPL6450 |
[Mm35b_P07R] Affymetrix Mouse Tiling 2.0R Set, Array 7 |
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Samples (43)
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This SuperSeries is composed of the following SubSeries: |
GSE11062 |
Genome-Wide Gli3 Binding Sites in the E11.5 Mouse Limb Bud |
GSE11063 |
Expression data from E11.5 mouse embryonic forelimbs - various mutant conditions or dissected limb domains |
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Relations |
BioProject |
PRJNA107069 |