The fully linked HTML version of this article has now been published.
Development ePress online publication date 18 Apr 2007
doi: 10.1242/dev.001966
Research article
Genomic characterization of Gli-activator targets in sonic hedgehog-mediated neural patterning
Steven A. Vokes,
Hongkai Ji,
Scott McCuine,
Toyoaki Tenzen,
Shane Giles,
Sheng Zhong,
William J.R. Longabaugh,
Eric H. Davidson,
Wing H. Wong,
and
Andrew P. McMahon*
* Author for correspondence (e-mail: mcmahon{at}mcb.harvard.edu)
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.
This article has been cited by other articles:
|
|
|
|
 
S. A. Vokes, H. Ji, W. H. Wong, and A. P. McMahon
A genome-scale analysis of the cis-regulatory circuitry underlying sonic hedgehog-mediated patterning of the mammalian limb
Genes & Dev.,
October 1, 2008;
22(19):
2651 - 2663.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Varjosalo and J. Taipale
Hedgehog: functions and mechanisms
Genes & Dev.,
September 15, 2008;
22(18):
2454 - 2472.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J King, L. Guasti, and E. Laufer
Hedgehog signalling in endocrine development and disease
J. Endocrinol.,
September 1, 2008;
198(3):
439 - 450.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Dessaud, A. P. McMahon, and J. Briscoe
Pattern formation in the vertebrate neural tube: a sonic hedgehog morphogen-regulated transcriptional network
Development,
August 1, 2008;
135(15):
2489 - 2503.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Xie, J. Cai, N.-Y. Chia, H. H. Ng, and S. Zhong
Cross-species de novo identification of cis-regulatory modules with GibbsModule: Application to gene regulation in embryonic stem cells
Genome Res.,
August 1, 2008;
18(8):
1325 - 1335.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Blaess, D. Stephen, and A. L. Joyner
Gli3 coordinates three-dimensional patterning and growth of the tectum and cerebellum by integrating Shh and Fgf8 signaling
Development,
June 15, 2008;
135(12):
2093 - 2103.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Eichberger, A. Kaser, C. Pixner, C. Schmid, S. Klingler, M. Winklmayr, C. Hauser-Kronberger, F. Aberger, and A.-M. Frischauf
GLI2-specific Transcriptional Activation of the Bone Morphogenetic Protein/Activin Antagonist Follistatin in Human Epidermal Cells
J. Biol. Chem.,
May 2, 2008;
283(18):
12426 - 12437.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2007
