Understanding the language of gene regulation 英文参考文献.docVIP

Meeting report Understanding the language of gene regulation Wynand Alkema* and Wyeth W Wasserman? Addresses: *Center for Genomics and Bioinformatics, Karolinska Institutet, Stockholm, Sweden. ?Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada. Correspondence: Wyeth W Wasserman. E-mail: wyeth@cmmt.ubc.ca Published: 18 June 2003 Genome Biology 2003, 4:327 The electronic version of this article is the complete one and can be found online at /2003/4/7/327 ? 2003 BioMed Central Ltd Modeling of the DNA-binding preferences of transcription A report on the Cold Spring Harbor Laboratory meeting ‘Systems Biology: genomic approaches to transcriptional regulation’, Cold Spring Harbor, USA, 6-9 March 2003. factors has so far mainly used single-order positional weight matrices - that is, matrices of the bases preferred at each position of a binding site assuming that the nucleotide observed at one position is independent of the nucleotide found at any other position. Recent published reports in which large collections of transcription-factor binding sites were generated and analyzed indicate that this underlying assumption is false. In a retrospective analysis of the collec- tions, Gary Stormo (Washington University, St. Louis, USA) explained that the underlying assumption is adequate in most cases, because inclusion of positional correlations gives only a marginal improvement in the specificity of binding-site pre- dictions. Stormo gave an inspiring call for researchers to use the techniques for generating large sets of transcription- factor binding sites to define quantitatively the target- nucleotide preferences of amino acids that directly interact with DNA. Using in vitro binding data for zinc-finger tran- scription factors, Stormo generated a quantitative matrix profile for t