INSECT: IN-silico SEarch for Co-occurring Transcription factors

MOTIVATION Transcriptional regulation occurs through the concerted actions of multiple transcription factors (TFs) that bind cooperatively to cis-regulatory modules (CRMs) of genes. These CRMs usually contain a variable number of transcription factor-binding sites (TFBSs) involved in related cellular and physiological processes. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) has been effective in detecting TFBSs and nucleosome location to identify potential CRMs in genome-wide studies. Although several attempts were previously reported to predict the potential binding of TFs at TFBSs within CRMs by comparing different ChIP-seq data, these have been hampered by excessive background, usually emerging as a consequence of experimental conditions. To understand these complex regulatory circuits, it would be helpful to have reliable and updated user-friendly tools to assist in the identification of TFBSs and CRMs for gene(s) of interest. RESULTS Here we present INSECT (IN-silico SEarch for Co-occurring Transcription factors), a novel web server for identifying potential TFBSs and CRMs in gene sequences. By combining several strategies, INSECT provides flexible analysis of multiple co-occurring TFBSs, by applying differing search schemes and restriction parameters. availability and implementation: INSECT is freely available as a web server at http://bioinformatics.ibioba-mpsp-conicet.gov.ar/INSECT .

[1]  E. Davidson,et al.  Modular cis-regulatory organization of developmentally expressed genes: two genes transcribed territorially in the sea urchin embryo, and additional examples. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[2]  P. V. von Hippel,et al.  Selection of DNA binding sites by regulatory proteins. Statistical-mechanical theory and application to operators and promoters. , 1987, Journal of molecular biology.

[3]  Matthias Wilmanns,et al.  Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers. , 2003, Genes & development.

[4]  Alexander E. Kel,et al.  TRANSFAC® and its module TRANSCompel®: transcriptional gene regulation in eukaryotes , 2005, Nucleic Acids Res..

[5]  E. Davidson,et al.  The hardwiring of development: organization and function of genomic regulatory systems. , 1997, Development.

[6]  Matthew W. Hahn,et al.  The evolution of transcriptional regulation in eukaryotes. , 2003, Molecular biology and evolution.

[7]  Martin C. Frith,et al.  Cluster-Buster: finding dense clusters of motifs in DNA sequences , 2003, Nucleic Acids Res..

[8]  P. Park ChIP–seq: advantages and challenges of a maturing technology , 2009, Nature Reviews Genetics.

[9]  Laurent Gil,et al.  Ensembl 2013 , 2012, Nucleic Acids Res..

[10]  Ting Wang,et al.  ENCODE whole-genome data in the UCSC Genome Browser , 2009, Nucleic Acids Res..

[11]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[12]  A. Sandelin,et al.  Applied bioinformatics for the identification of regulatory elements , 2004, Nature Reviews Genetics.

[13]  Ole Winther,et al.  JASPAR, the open access database of transcription factor-binding profiles: new content and tools in the 2008 update , 2007, Nucleic Acids Res..

[14]  P. V. von Hippel,et al.  Selection of DNA binding sites by regulatory proteins. , 1988, Trends in biochemical sciences.

[15]  Peter Van Loo,et al.  Computational methods for the detection of cis-regulatory modules , 2009, Briefings Bioinform..

[16]  D. S. Fields,et al.  Specificity, free energy and information content in protein-DNA interactions. , 1998, Trends in biochemical sciences.

[17]  Wyeth W. Wasserman,et al.  TFBS: Computational framework for transcription factor binding site analysis , 2002, Bioinform..

[18]  M. Blumenfeld,et al.  Analysis of the distribution of binding sites for a tissue-specific transcription factor in the vertebrate genome. , 1997, Journal of molecular biology.

[19]  Martha L. Bulyk,et al.  UniPROBE: an online database of protein binding microarray data on protein–DNA interactions , 2008, Nucleic Acids Res..

[20]  Megan F. Cole,et al.  Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells , 2005, Cell.

[21]  Kathleen Marchal,et al.  ModuleDigger: an itemset mining framework for the detection of cis-regulatory modules , 2009, BMC Bioinformatics.

[22]  David Haussler,et al.  ENCODE whole-genome data in the UCSC genome browser (2011 update) , 2010, Nucleic Acids Res..

[23]  A. Clark,et al.  Evolution of transcription factor binding sites in Mammalian gene regulatory regions: conservation and turnover. , 2002, Molecular biology and evolution.

[24]  X. Chen,et al.  The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells , 2006, Nature Genetics.

[25]  P. Robson,et al.  Transcriptional Regulation of Nanog by OCT4 and SOX2* , 2005, Journal of Biological Chemistry.

[26]  A. Reményi,et al.  Crystal structure of a POU/HMG/DNA ternary complex , 2003 .

[27]  Peter M. Haverty,et al.  MotifViz: an analysis and visualization tool for motif discovery , 2004, Nucleic Acids Res..

[28]  Kathleen Marchal,et al.  Unveiling combinatorial regulation through the combination of ChIP information and in silico cis-regulatory module detection , 2012, Nucleic acids research.