De novo motif identification improves the accuracy of predicting transcription factor binding sites in ChIP-Seq data analysis

Dramatic progress in the development of next-generation sequencing technologies has enabled accurate genome-wide characterization of the binding sites of DNA-associated proteins. This technique, baptized as ChIP-Seq, uses a combination of chromatin immunoprecipitation and massively parallel DNA sequ...

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Bibliographic Details
Published in:Nucleic acids research 2010-06, Vol.38 (11), p.e126-e126
Main Authors: Boeva, Valentina, Surdez, Didier, Guillon, Noëlle, Tirode, Franck, Fejes, Anthony P, Delattre, Olivier, Barillot, Emmanuel
Format: Article
Language:English
Subjects:
Algorithms
Base Sequence
Binding Sites
Biochemistry, Molecular Biology
Cancer
Cell Line, Tumor
Chromatin Immunoprecipitation - methods
Consensus Sequence
Genomics
Humans
Life Sciences
Methods Online
Molecular biology
Oncogene Proteins, Fusion - metabolism
Proto-Oncogene Protein c-fli-1 - metabolism
Regulatory Elements, Transcriptional
RNA-Binding Protein EWS
Sequence Analysis, DNA
Transcription Factors - metabolism
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Summary:Dramatic progress in the development of next-generation sequencing technologies has enabled accurate genome-wide characterization of the binding sites of DNA-associated proteins. This technique, baptized as ChIP-Seq, uses a combination of chromatin immunoprecipitation and massively parallel DNA sequencing. Other published tools that predict binding sites from ChIP-Seq data use only positional information of mapped reads. In contrast, our algorithm MICSA (Motif Identification for ChIP-Seq Analysis) combines this source of positional information with information on motif occurrences to better predict binding sites of transcription factors (TFs). We proved the greater accuracy of MICSA with respect to several other tools by running them on datasets for the TFs NRSF, GABP, STAT1 and CTCF. We also applied MICSA on a dataset for the oncogenic TF EWS-FLI1. We discovered >2000 binding sites and two functionally different binding motifs. We observed that EWS-FLI1 can activate gene transcription when (i) its binding site is located in close proximity to the gene transcription start site (up to approximately 150 kb), and (ii) it contains a microsatellite sequence. Furthermore, we observed that sites without microsatellites can also induce regulation of gene expression--positively as often as negatively--and at much larger distances (up to approximately 1 Mb).
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkq217