PMID- 19890324
OWN - NLM
STAT- MEDLINE
DCOM- 20091223
LR  - 20211020
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Linking)
VI  - 462
IP  - 7269
DP  - 2009 Nov 5
TI  - Combinatorial binding predicts spatio-temporal cis-regulatory activity.
PG  - 65-70
LID - 10.1038/nature08531 [doi]
AB  - Development requires the establishment of precise patterns of gene expression, 
      which are primarily controlled by transcription factors binding to cis-regulatory 
      modules. Although transcription factor occupancy can now be identified at 
      genome-wide scales, decoding this regulatory landscape remains a daunting 
      challenge. Here we used a novel approach to predict spatio-temporal 
      cis-regulatory activity based only on in vivo transcription factor binding and 
      enhancer activity data. We generated a high-resolution atlas of cis-regulatory 
      modules describing their temporal and combinatorial occupancy during Drosophila 
      mesoderm development. The binding profiles of cis-regulatory modules with 
      characterized expression were used to train support vector machines to predict 
      five spatio-temporal expression patterns. In vivo transgenic reporter assays 
      demonstrate the high accuracy of these predictions and reveal an unanticipated 
      plasticity in transcription factor binding leading to similar expression. This 
      data-driven approach does not require previous knowledge of transcription factor 
      sequence affinity, function or expression, making it widely applicable.
FAU - Zinzen, Robert P
AU  - Zinzen RP
AD  - European Molecular Biology Laboratory, D-69117 Heidelberg, Germany.
FAU - Girardot, Charles
AU  - Girardot C
FAU - Gagneur, Julien
AU  - Gagneur J
FAU - Braun, Martina
AU  - Braun M
FAU - Furlong, Eileen E M
AU  - Furlong EE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Artificial Intelligence
MH  - Chromatin Immunoprecipitation
MH  - Conserved Sequence/genetics
MH  - Databases, Genetic
MH  - Drosophila melanogaster/*embryology/*genetics
MH  - Enhancer Elements, Genetic/genetics
MH  - *Gene Expression Regulation, Developmental/genetics
MH  - Genes, Reporter/genetics
MH  - Mesoderm/embryology/metabolism
MH  - *Models, Genetic
MH  - Protein Binding
MH  - Time Factors
MH  - Transcription Factors/*metabolism
EDAT- 2009/11/06 06:00
MHDA- 2009/12/24 06:00
CRDT- 2009/11/06 06:00
PHST- 2009/07/21 00:00 [received]
PHST- 2009/09/22 00:00 [accepted]
PHST- 2009/11/06 06:00 [entrez]
PHST- 2009/11/06 06:00 [pubmed]
PHST- 2009/12/24 06:00 [medline]
AID - nature08531 [pii]
AID - 10.1038/nature08531 [doi]
PST - ppublish
SO  - Nature. 2009 Nov 5;462(7269):65-70. doi: 10.1038/nature08531.