PMID- 19483094
OWN - NLM
STAT- MEDLINE
DCOM- 20090825
LR  - 20211020
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 37
IP  - 13
DP  - 2009 Jul
TI  - Measuring spatial preferences at fine-scale resolution identifies known and novel 
      cis-regulatory element candidates and functional motif-pair relationships.
PG  - e92
LID - 10.1093/nar/gkp423 [doi]
AB  - 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.
FAU - Yokoyama, Ken Daigoro
AU  - Yokoyama KD
AD  - Biology Department, Institute for Genome Sciences and Policy, Duke University, 
      Durham, NC 27708, USA.
FAU - Ohler, Uwe
AU  - Ohler U
FAU - Wray, Gregory A
AU  - Wray GA
LA  - eng
GR  - 5P50-GM-081883/GM/NIGMS NIH HHS/United States
GR  - HG004065/HG/NHGRI NIH HHS/United States
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090529
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Binding Sites
MH  - Consensus Sequence
MH  - Humans
MH  - Mice
MH  - Models, Genetic
MH  - *Promoter Regions, Genetic
MH  - Regression Analysis
MH  - *Sequence Analysis, DNA
MH  - Transcription Factors/*metabolism
MH  - Transcription Initiation Site
PMC - PMC2715254
EDAT- 2009/06/02 09:00
MHDA- 2009/08/26 09:00
PMCR- 2009/06/02
CRDT- 2009/06/02 09:00
PHST- 2009/06/02 09:00 [entrez]
PHST- 2009/06/02 09:00 [pubmed]
PHST- 2009/08/26 09:00 [medline]
PHST- 2009/06/02 00:00 [pmc-release]
AID - gkp423 [pii]
AID - 10.1093/nar/gkp423 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2009 Jul;37(13):e92. doi: 10.1093/nar/gkp423. Epub 2009 May 
      29.