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

Item Type:	Article
Title:	Measuring spatial preferences at fine-scale resolution identifies known and novel cis-regulatory element candidates and functional motif-pair relationships
Creators Name:	Yokoyama, K.D. and Ohler, U. and Wray, G.A.
Abstract:	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.
Keywords:	Base Sequence, Binding Sites, Consensus Sequence, DNA Sequence Analysis, Genetic Models, Genetic Promoter Regions, Regression Analysis, Transcription Factors, Transcription Initiation Site, Animals, Mice
Source:	Nucleic Acids Research
ISSN:	0305-1048
Publisher:	Oxford University Press
Volume:	37
Number:	13
Page Range:	e92
Date:	July 2009
Official Publication:	https://doi.org/10.1093/nar/gkp423
PubMed:	View item in PubMed

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