title: Correlated evolution of transcription factors and their binding sites.
abstract: BACKGROUND
  The interaction between transcription factor (TF) and transcription factor binding site (TFBS) is essential for gene regulation. Mutation in either the TF or the TFBS may weaken their interaction and thus result in abnormalities. To maintain such vital interaction, a mutation in one of the interacting partners might be compensated by a corresponding mutation in its binding partner during the course of evolution. Confirming this co-evolutionary relationship will guide us in designing protein sequences to target a specific DNA sequence or in predicting TFBS for poorly studied proteins, or even correcting and rescuing disease mutations in clinical applications.
  
  
  RESULTS
  Based on six, publicly available, experimentally validated TF-TFBS binding datasets for the basic Helix-Loop-Helix (bHLH) family, Homeo family, High-Mobility Group (HMG) family and Transient Receptor Potential channels (TRP) family, we showed that the evolutions of the TFs and their TFBSs are significantly correlated across eukaryotes. We further developed a mutual information-based method to identify co-evolved protein residues and DNA bases. This research sheds light on the dynamic relationship between TF and TFBS during their evolution. The same principle and strategy can be applied to co-evolutionary studies on protein-DNA interactions in other protein families.
  
  
  BACKGROUND
  All the datasets, scripts and other related files have been made freely available at: http://jjwanglab.org/co-evo.
  
  
  BACKGROUND
  junwen@uw.edu.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors: Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors: Shu
authors: S
authors: Yang
authors: Hari Krishna
authors: HK
authors: Yalamanchili
authors: Xinran
authors: X
authors: Li
authors: Kwok-Ming
authors: KM
authors: Yao
authors: Pak Chung
authors: PC
authors: Sham
authors: Michael Q
authors: MQ
authors: Zhang
authors: Junwen
authors: J
authors: Wang
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D019143:Evolution, Molecular; D006801:Humans; D050436:Regulatory Elements, Transcriptional; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; D004247:DNA