title: Accumulation of CTCF-binding sites drives expression divergence between tandemly duplicated genes in humans.
abstract: BACKGROUND
  During eukaryotic genome evolution, tandem gene duplication is the most frequent event giving rise to clustered gene families. However, how expression divergence between tandemly duplicated genes has emerged and maintained remain unclear. In particular, it is unknown if epigenetic regulators have been involved in the process.
  
  
  RESULTS
  We demonstrate that CCCTC-binding factor (CTCF), the master epigenetic regulator and the only known insulator protein in humans, has played a predominant role in generating divergence in both expression profiles and expression levels between adjacent paralogs in the human genome. This phenomenon was not observed for non-paralogous adjacent genes. After tandem duplication events, CTCF-binding sites gradually accumulate between paralogs. This trend was more prominent for genes involved in particular functions.
  
  
  CONCLUSIONS
  The accumulation of CTCF-binding sites drives expression divergence of tandemly duplicated genes. This process is likely targeted by natural selection. Our study reveals the importance of CTCF to the evolution of animal diversity and complexity.
authors.forename: Ben-Yang
authors.initials: BY
authors.lastname: Liao
authors.forename: Andrew
authors.initials: A
authors.lastname: Chang
mesh_terms: D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D019143:Evolution, Molecular; D020440:Gene Duplication; D015894:Genome, Human; D023281:Genomics / Q000379:methods*; D006801:Humans; D005810:Multigene Family; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012641:Selection, Genetic; D017423:Sequence Analysis, RNA; D020080:Tandem Repeat Sequences
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D012097:Repressor Proteins