Computational prediction and experimental validation of novel Hedgehog-responsive enhancers linked to genes of the Hedgehog pathway

BMC Developmental Biology
Katherine GurdzielDeborah L Gumucio

Abstract

The Hedgehog (Hh) signaling pathway, acting through three homologous transcription factors (GLI1, GLI2, GLI3) in vertebrates, plays multiple roles in embryonic organ development and adult tissue homeostasis. At the level of the genome, GLI factors bind to specific motifs in enhancers, some of which are hundreds of kilobases removed from the gene promoter. These enhancers integrate the Hh signal in a context-specific manner to control the spatiotemporal pattern of target gene expression. Importantly, a number of genes that encode Hh pathway molecules are themselves targets of Hh signaling, allowing pathway regulation by an intricate balance of feed-back activation and inhibition. However, surprisingly few of the critical enhancer elements that control these pathway target genes have been identified despite the fact that such elements are central determinants of Hh signaling activity. Recently, ChIP studies have been carried out in multiple tissue contexts using mouse models carrying FLAG-tagged GLI proteins (GLI(FLAG)). Using these datasets, we tested whether a meta-analysis of GLI binding sites, coupled with a machine learning approach, could reveal genomic features that could be used to empirically identify Hh-regulated enhanc...Continue Reading

References

Sep 3, 1996·Proceedings of the National Academy of Sciences of the United States of America·S NonchevR Krumlauf
Mar 13, 1999·The Journal of Biological Chemistry·P DaiS Ishii
Mar 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·S H ShinL G Biesecker
Jan 2, 2003·Current Topics in Developmental Biology·Andrew P McMahonClifford J Tabin
Nov 14, 2003·The Biochemical Journal·Fahimeh RahnamaPeter G Zaphiropoulos
Dec 19, 2003·Nucleic Acids Research·Axel ViselGregor Eichele
Jun 3, 2004·Genome Research·Gavin E CrooksSteven E Brenner
Feb 28, 2007·Genome Biology·Shobhit GuptaWilliam Stafford Noble
Apr 17, 2007·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Galina V Aglyamova, Seema Agarwala
May 17, 2007·Genes & Development·David C Martinelli, Chen-Ming Fan
Apr 26, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Nicole Santos, Jeremy F Reiter
Sep 17, 2008·Genes & Development·Markku Varjosalo, Jussi Taipale
Dec 17, 2008·Developmental Cell·Jin Jiang, Chi-Chung Hui
Aug 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Karel F LiemKathryn V Anderson
Dec 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jynho KimPhilip A Beachy
Jan 15, 2010·BMC Molecular Biology·Martina WinklmayrAnna-Maria Frischauf
Apr 17, 2010·Nature Reviews. Genetics·Sarah C Goetz, Kathryn V Anderson
May 4, 2010·Nature Biotechnology·Cory Y McLeanGill Bejerano
May 13, 2010·Proceedings of the National Academy of Sciences of the United States of America·Eunice Y LeeMatthew P Scott
Sep 17, 2010·Genes & Development·Philip A BeachyChristian Siebold
Nov 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·Menno P CreyghtonRudolf Jaenisch
Jan 27, 2011·PLoS Biology·Graciana Diez-RouxAndrea Ballabio
Apr 14, 2011·Bioinformatics·Philip Machanick, Timothy L Bailey
May 6, 2011·Bioinformatics·Timothy L Bailey
Aug 31, 2011·Genome Research·Dongwon LeeMichael A Beer
May 23, 2012·Nucleic Acids Research·Timothy L Bailey, Philip Machanick
Jun 9, 2012·Genes & Development·Adrian CreangaPhilip A Beachy
Aug 8, 2012·Nature Reviews. Genetics·François Spitz, Eileen E M Furlong
Sep 8, 2012·Nature·UNKNOWN ENCODE Project Consortium
May 31, 2013·Nature Reviews. Molecular Cell Biology·James Briscoe, Pascal P Thérond
Jun 19, 2013·Nucleic Acids Research·Christopher Fletez-BrantMichael A Beer
Feb 14, 2014·Journal of Cell Science·Petra JakobsKay Grobe
Aug 19, 2014·Trends in Biochemical Sciences·Matthew SlatteryRemo Rohs
Sep 4, 2014·Development·Ralitsa Petrova, Alexandra L Joyner

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Citations

Mar 2, 2016·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Katherine GurdzielDeborah L Gumucio
Aug 9, 2020·The Biochemical Journal·Ezequiel J TolosaMartin E Fernandez-Zapico

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Methods Mentioned

BETA
immunoprecipitation
ChIP-chip
ChIP
ChIP-seq
in silico methods
PCR
transfection
Assay

Software Mentioned

DREME
kmer
LDwGBM
MEME
MCA
ChIP
Centrimo
NPwGBM
custom Perl
Module Cluster Analysis ( MCA

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