A nucleosome-guided map of transcription factor binding sites in yeast.

dc.contributor.author

Narlikar, Leelavati

dc.contributor.author

Gordân, Raluca

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Hartemink, Alexander J

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Miyano, Satoru

dc.coverage.spatial

United States

dc.date.accessioned

2017-08-01T20:51:43Z

dc.date.issued

2007-11

dc.description.abstract

Finding functional DNA binding sites of transcription factors (TFs) throughout the genome is a crucial step in understanding transcriptional regulation. Unfortunately, these binding sites are typically short and degenerate, posing a significant statistical challenge: many more matches to known TF motifs occur in the genome than are actually functional. However, information about chromatin structure may help to identify the functional sites. In particular, it has been shown that active regulatory regions are usually depleted of nucleosomes, thereby enabling TFs to bind DNA in those regions. Here, we describe a novel motif discovery algorithm that employs an informative prior over DNA sequence positions based on a discriminative view of nucleosome occupancy. When a Gibbs sampling algorithm is applied to yeast sequence-sets identified by ChIP-chip, the correct motif is found in 52% more cases with our informative prior than with the commonly used uniform prior. This is the first demonstration that nucleosome occupancy information can be used to improve motif discovery. The improvement is dramatic, even though we are using only a statistical model to predict nucleosome occupancy; we expect our results to improve further as high-resolution genome-wide experimental nucleosome occupancy data becomes increasingly available.

dc.identifier

https://www.ncbi.nlm.nih.gov/pubmed/17997593

dc.identifier

07-PLCB-RA-0358

dc.identifier.eissn

1553-7358

dc.identifier.uri

https://hdl.handle.net/10161/15157

dc.language

eng

dc.publisher

Public Library of Science (PLoS)

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PLoS Comput Biol

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10.1371/journal.pcbi.0030215

dc.subject

Binding Sites

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DNA, Fungal

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Nucleosomes

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Oligonucleotide Array Sequence Analysis

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Protein Binding

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Protein Interaction Mapping

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Saccharomyces cerevisiae

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Saccharomyces cerevisiae Proteins

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Sequence Analysis, DNA

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Transcription Factors

dc.title

A nucleosome-guided map of transcription factor binding sites in yeast.

dc.type

Journal article

duke.contributor.orcid

Hartemink, Alexander J|0000-0002-1292-2606

pubs.author-url

https://www.ncbi.nlm.nih.gov/pubmed/17997593

pubs.begin-page

e215

pubs.issue

11

pubs.organisational-group

Basic Science Departments

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Biostatistics & Bioinformatics

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Computer Science

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Duke

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Molecular Genetics and Microbiology

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School of Medicine

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Trinity College of Arts & Sciences

pubs.publication-status

Published

pubs.volume

3

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