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PMID:17442700

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Citation

Vokes, SA, Ji, H, McCuine, S, Tenzen, T, Giles, S, Zhong, S, Longabaugh, WJ, Davidson, EH, Wong, WH and McMahon, AP (2007) Genomic characterization of Gli-activator targets in sonic hedgehog-mediated neural patterning. Development 134:1977-89

Abstract

Sonic hedgehog (Shh) acts as a morphogen to mediate the specification of distinct cell identities in the ventral neural tube through a Gli-mediated (Gli1-3) transcriptional network. Identifying Gli targets in a systematic fashion is central to the understanding of the action of Shh. We examined this issue in differentiating neural progenitors in mouse. An epitope-tagged Gli-activator protein was used to directly isolate cis-regulatory sequences by chromatin immunoprecipitation (ChIP). ChIP products were then used to screen custom genomic tiling arrays of putative Hedgehog (Hh) targets predicted from transcriptional profiling studies, surveying 50-150 kb of non-transcribed sequence for each candidate. In addition to identifying expected Gli-target sites, the data predicted a number of unreported direct targets of Shh action. Transgenic analysis of binding regions in Nkx2.2, Nkx2.1 (Titf1) and Rab34 established these as direct Hh targets. These data also facilitated the generation of an algorithm that improved in silico predictions of Hh target genes. Together, these approaches provide significant new insights into both tissue-specific and general transcriptional targets in a crucial Shh-mediated patterning process.

Links

PubMed Online version:10.1242/dev.001966

Keywords

Amino Acid Motifs; Animals; Body Patterning; Chromatin Immunoprecipitation; Epitopes/metabolism; Gene Expression Profiling; Genome; Hedgehog Proteins/metabolism; Hedgehog Proteins/physiology; Kruppel-Like Transcription Factors/genetics; Kruppel-Like Transcription Factors/physiology; Mice; Mice, Transgenic; NIH 3T3 Cells; Neurons/cytology; Neurons/metabolism; Stem Cells/cytology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:GLI1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:GLI1

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(MGI:MGI:105373)|has_input:(MGI:MGI:97347)|has_input:(MGI:MGI:108067)|has_input:(MGI:MGI:104606)

Seeded From UniProt

complete

MOUSE:SHH

acts_upstream_of_or_within

GO:0021904: dorsal/ventral neural tube patterning

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GLI1

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:GLI1

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:GLI1

enables

GO:0000981: DNA-binding transcription factor activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:GLI1

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

has_regulation_target:(MGI:MGI:105373)|has_regulation_target:(MGI:MGI:97347)|has_regulation_target:(MGI:MGI:108067)|has_regulation_target:(MGI:MGI:104606)

Seeded From UniProt

complete


See also

References

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