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Cracking the Second Genetic Code
Author(s) -
Hughes Tim
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.262.2
Subject(s) - computational biology , dna , modularity (biology) , biology , dna microarray , dna binding site , genetic code , genetics , single stranded binding protein , genome , binding site , dna binding protein , hmg box , dna sequencing , gene , protein–dna interaction , evolutionary biology , gene expression , transcription factor , promoter
The interaction specificities between proteins and DNA has been termed the “second genetic code”. Despite the central importance of DNA‐binding activities to cell biology, physiology, development, and evolution, the complete binding activity of only a small minority of DNA‐binding proteins has been experimentally established. We have used microarrays to examine the binding specificities of over 300 mouse DNA‐binding proteins representing 23 different structural classes. Our results reveal a surprisingly complex landscape of DNA‐binding activities, with most proteins possessing unique and complex binding profiles, such that consensus and position weight matrix representations can have both low specificity and sensitivity. We propose that the evolutionary success of many DNA‐binding protein families, typically attributed to modularity in spatial expression or protein‐protein interactions, is also be due to diversity and malleability in DNA sequence recognition, which in turn could facilitate evolution of regulatory programs. We anticipate that the data resulting from this effort will be invaluable for understanding both gene regulation and genome evolution.