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Phylogenetic footprinting : ウィキペディア英語版
Phylogenetic footprinting

Phylogenetic footprinting is a technique used to identify transcription factor binding sites (TFBS) within a non-coding region of DNA of interest by comparing it to the orthologous sequence in different species. When this technique is used with a large number of closely related species, this is called phylogenetic shadowing.〔Phylogenetic Shadowing of Primate Sequences to Find Functional Regions of the Human Genome 〕
Researchers have found that non-coding pieces of DNA contain binding sites for regulatory proteins that govern the spatiotemporal expression of genes. These transcription factor binding sites (TFBS), or regulatory motifs, have proven hard to identify, primarily because they are short in length, and can show sequence variation. The importance of understanding transcriptional regulation to many fields of biology has led researchers to develop strategies for predicting the presence of TFBS, many of which have led to publicly available databases. One such technique is Phylogenetic Footprinting.
Phylogenetic footprinting relies upon two major concepts:
# The function and DNA binding preferences of transcription factors are well-conserved between diverse species.
# Important non-coding DNA sequences that are essential for regulating gene expression will show differential selective pressure. A slower rate of change occurs in TFBS than in other, less critical, parts of the non-coding genome.〔Neph, S. and Tompa, M. 2006. MicroFootPrinter: a tool for phylogenetic footprinting in prokaryotic genomes. ''Nucleic Acids Research''. 34: 366-368〕
==History ==

Phylogenetic footprinting was first used and published by Tagle et al. in 1988, which allowed researchers to predict evolutionary conserved cis-regulatory elements responsible for embryonic ε and γ globulin gene expression in primates.〔Tagle, D. A., Koop, B. F., Goodman, M., Slightom, J. L., Hess, D., and Jones, R. T. 1988. Embryonic ε and γ globin genes of a prosimian primate (Galago crassicaudatis): nucleotide and amino acid sequences, developmental regulation, and phylogenetic footprints. ''J. Mol. Biol.'' 203:439-455.〕
Before phylogenetic footprinting, DNase footprinting was used, where protein would be bound to DNA transcription factor binding sites (TFBS) protecting it from DNase digestion. One of the problems with this technique was the amount of time and labor it would take. Unlike DNase footprinting, phylogenetic footprinting relies on evolutionary constraints within the genome, with the "important" parts of the sequence being conserved among the different species.〔Zhang, Z. and Gerstein, M. 2003. Of mice and men: phylogenetic footprinting aids the discovery of regulatory elements.''J. Biol.''2:11-11.4〕

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