Title
Predicting functionality of protein-DNA interactions by integrating diverse evidence.
Abstract
Chromatin immunoprecipitation (ChIP-chip) experiments enable capturing physical interactions between regulatory proteins and DNA in vivo. However, measurement of chromatin binding alone is not sufficient to detect regulatory interactions. A detected binding event may not be biologically relevant, or a known regulatory interaction might not be observed under the growth conditions tested so far. To correctly identify physical interactions between transcription factors (TFs) and genes and to determine their regulatory implications under various experimental conditions, we integrated ChIP-chip data with motif binding sites, nucleosome occupancy and mRNA expression datasets within a probabilistic framework. This framework was specifically tailored for the identification of functional and non-functional DNA binding events. Using this, we estimate that only 50% of condition-specific protein-DNA binding in budding yeast is functional. We further investigated the molecular factors determining the functionality of protein-DNA interactions under diverse growth conditions. Our analysis suggests that the functionality of binding is highly condition-specific and highly dependent on the presence of specific cofactors. Hence, the joint analysis of both, functional and non-functional DNA binding, may lend important new insights into transcriptional regulation.
Year
DOI
Venue
2009
10.1093/bioinformatics/btp213
Bioinformatics
Keywords
Field
DocType
non-functional dna,regulatory interaction,regulatory implication,chromatin immunoprecipitation,diverse evidence,motif binding site,predicting functionality,dna interaction,regulatory protein,condition-specific protein,binding event,physical interaction,gene expression,binding sites,dna binding proteins,gene expression profiling,transcription regulation,binding site,chip,protein dna interaction,transcription factor
Chromatin binding,DNA binding site,Biology,ChIA-PET,ChIP-sequencing,Bioinformatics,Chromatin immunoprecipitation,Nucleosome,Protein–DNA interaction,Transcription factor
Journal
Volume
Issue
ISSN
25
12
1367-4811
Citations 
PageRank 
References 
12
0.99
9
Authors
4
Name
Order
Citations
PageRank
Duygu Ucar134719.69
Andreas Beyer29910.92
Srinivasan Parthasarathy34666375.76
Christopher Workman429541.80