@ARTICLE{Nam2010,
  author = {Nam, Jongmin and Dong, Ping and Tarpine, Ryan and Istrail, Sorin
	and Davidson, Eric H.},
  title = {Functional cis-regulatory genomics for systems biology},
  journal = {Proceedings of the National Academy of Sciences},
  year = {2010},
  volume = {107},
  pages = {3930--3935},
  number = {8},
  abstract = {Gene expression is controlled by interactions between trans-regulatory
	factors and cis-regulatory DNA sequences, and these interactions
	constitute the essential functional linkages of gene regulatory networks
	(GRNs). Validation of GRN models requires experimental cis-regulatory
	tests of predicted linkages to authenticate their identities and
	proposed functions. However, cis-regulatory analysis is, at present,
	at a severe bottleneck in genomic system biology because of the demanding
	experimental methodologies currently in use for discovering cis-regulatory
	modules (CRMs), in the genome, and for measuring their activities.
	Here we demonstrate a high-throughput approach to both discovery
	and quantitative characterization of CRMs. The unique aspect is use
	of DNA sequence tags to ???barcode??? CRM expression constructs,
	which can then be mixed, injected together into sea urchin eggs,
	and subsequently deconvolved. This method has increased the rate
	of cis-regulatory analysis by >100-fold compared with conventional
	one-by-one reporter assays. The utility of the DNA-tag reporters
	was demonstrated by the rapid discovery of 81 active CRMs from 37
	previously unexplored sea urchin genes. We then obtained simultaneous
	high-resolution temporal characterization of the regulatory activities
	of more than 80 CRMs. On average 2???3 CRMs were discovered per gene.
	Comparison of endogenous gene expression profiles with those of the
	CRMs recovered from each gene showed that, for most cases, at least
	one CRM is active in each phase of endogenous expression, suggesting
	that CRM recovery was comprehensive. This approach will qualitatively
	alter the practice of GRN construction as well as validation, and
	will impact many additional areas of regulatory system biology.},
  date = {February 23, 2010},
  doi = {10.1073/pnas.1000147107},
  owner = {Derek},
  timestamp = {2012.05.08},
  url = {http://www.brown.edu/Research/Istrail_Lab/papers/PNAS-2010-Nam-3930-5.pdf},
  category = {Regulatory Genomics}
}