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Measuring spatial preferences at fine-scale resolution identifies known and novel cis-regulatory element candidates and functional motif-pair relationships.

Publication ,  Journal Article
Yokoyama, KD; Ohler, U; Wray, GA
Published in: Nucleic Acids Res
July 2009

Transcriptional regulation is mediated by the collective binding of proteins called transcription factors to cis-regulatory elements. A handful of factors are known to function at particular distances from the transcription start site, although the extent to which this occurs is not well understood. Spatial dependencies can also exist between pairs of binding motifs, facilitating factor-pair interactions. We sought to determine to what extent spatial preferences measured at high-scale resolution could be utilized to predict cis-regulatory elements as well as motif-pairs binding interacting proteins. We introduce the 'motif positional function' model which predicts spatial biases using regression analysis, differentiating noise from true position-specific overrepresentation at single-nucleotide resolution. Our method predicts 48 consensus motifs exhibiting positional enrichment within human promoters, including fourteen motifs without known binding partners. We then extend the model to analyze distance preferences between pairs of motifs. We find that motif-pairs binding interacting factors often co-occur preferentially at multiple distances, with intervals between preferred distances often corresponding to the turn of the DNA double-helix. This offers a novel means by which to predict sequence elements with a collective role in gene regulation.

Duke Scholars

Published In

Nucleic Acids Res

DOI

EISSN

1362-4962

Publication Date

July 2009

Volume

37

Issue

13

Start / End Page

e92

Location

England

Related Subject Headings

  • Transcription Initiation Site
  • Transcription Factors
  • Sequence Analysis, DNA
  • Regression Analysis
  • Promoter Regions, Genetic
  • Models, Genetic
  • Mice
  • Humans
  • Developmental Biology
  • Consensus Sequence
 

Citation

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ICMJE
MLA
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Yokoyama, K. D., Ohler, U., & Wray, G. A. (2009). Measuring spatial preferences at fine-scale resolution identifies known and novel cis-regulatory element candidates and functional motif-pair relationships. Nucleic Acids Res, 37(13), e92. https://doi.org/10.1093/nar/gkp423
Yokoyama, Ken Daigoro, Uwe Ohler, and Gregory A. Wray. “Measuring spatial preferences at fine-scale resolution identifies known and novel cis-regulatory element candidates and functional motif-pair relationships.Nucleic Acids Res 37, no. 13 (July 2009): e92. https://doi.org/10.1093/nar/gkp423.
Yokoyama, Ken Daigoro, et al. “Measuring spatial preferences at fine-scale resolution identifies known and novel cis-regulatory element candidates and functional motif-pair relationships.Nucleic Acids Res, vol. 37, no. 13, July 2009, p. e92. Pubmed, doi:10.1093/nar/gkp423.
Journal cover image

Published In

Nucleic Acids Res

DOI

EISSN

1362-4962

Publication Date

July 2009

Volume

37

Issue

13

Start / End Page

e92

Location

England

Related Subject Headings

  • Transcription Initiation Site
  • Transcription Factors
  • Sequence Analysis, DNA
  • Regression Analysis
  • Promoter Regions, Genetic
  • Models, Genetic
  • Mice
  • Humans
  • Developmental Biology
  • Consensus Sequence