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Cross-species de novo identification of cis-regulatory modules with GibbsModule: application to gene regulation in embryonic stem cells.
- Source :
-
Genome research [Genome Res] 2008 Aug; Vol. 18 (8), pp. 1325-35. Date of Electronic Publication: 2008 May 15. - Publication Year :
- 2008
-
Abstract
- We introduce the GibbsModule algorithm for de novo detection of cis-regulatory motifs and modules in eukaryote genomes. GibbsModule models the coexpressed genes within one species as sharing a core cis-regulatory motif and each homologous gene group as sharing a homologous cis-regulatory module (CRM), characterized by a similar composition of motifs. Without using a predetermined alignment result, GibbsModule iteratively updates the core motif shared by coexpressed genes and traces the homologous CRMs that contain the core motif. GibbsModule achieved substantial improvements in both precision and recall as compared with peer algorithms on a number of synthetic and real data sets. Applying GibbsModule to analyze the binding regions of the Krüppel-like factor (KLF) transcription factor in embryonic stem cells (ESCs), we discovered a motif that differs from a previously published KLF motif identified by a SELEX experiment, but the new motif is consistent with mutagenesis analysis. The SOX2 motif was found to be a collaborating motif to the KLF motif in ESCs. We used quantitative chromatin immunoprecipitation (ChIP) analysis to test whether GibbsModule could distinguish functional and nonfunctional binding sites. All seven tested binding sites in GibbsModule-predicted CRMs had higher ChIP signals as compared with the other seven tested binding sites located outside of predicted CRMs. GibbsModule is available at (http://biocomp.bioen.uiuc.edu/GibbsModule).
- Subjects :
- Animals
Binding Sites
Cells, Cultured
DNA-Binding Proteins metabolism
Enhancer Elements, Genetic
Gene Expression Regulation
Genomics
HMGB Proteins metabolism
Humans
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors metabolism
Mice
Muscle Cells metabolism
SOXB1 Transcription Factors
Algorithms
Embryonic Stem Cells metabolism
Regulatory Elements, Transcriptional
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1088-9051
- Volume :
- 18
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Genome research
- Publication Type :
- Academic Journal
- Accession number :
- 18490265
- Full Text :
- https://doi.org/10.1101/gr.072769.107