cis-Regulatory Remodeling of the SCL Locus during Vertebrate Evolution

Research output: Contribution to journalArticle


  • B Goettgens
  • R Ferreira
  • MJ Sanchez
  • S Ishibashi
  • J Li
  • D Spensberger
  • P Lefevre
  • K Ottersbach
  • M Chapman
  • S Kinston
  • K Knezevic
  • GA Follows
  • E Amaya
  • AR Green

Colleges, School and Institutes


Development progresses through a sequence of cellular identities which are determined by the activities of networks of transcription factor genes. Alterations in cis-regulatory elements of these genes play a major role in evolutionary change, but little is known about the mechanisms responsible for maintaining conserved patterns of gene expression. We have studied the evolution of cis-regulatory mechanisms controlling the SCL gene, which encodes a key transcriptional regulator of blood, vasculature, and brain development and exhibits conserved function and pattern of expression throughout vertebrate evolution. SCL cis-regulatory elements are conserved between frog and chicken but accrued alterations at an accelerated rate between 310 and 200 million years ago, with subsequent fixation of a new cis-regulatory pattern at the beginning of the mammalian radiation. As a consequence, orthologous elements shared by mammals and lower vertebrates exhibit functional differences and binding site turnover between widely separated cis-regulatory modules. However, the net effect of these alterations is constancy of overall regulatory inputs and of expression pattern. Our data demonstrate remarkable cis-regulatory remodelling across the SCL locus and indicate that stable patterns of expression can mask extensive regulatory change. These insights illuminate our understanding of vertebrate evolution.


Original languageEnglish
Pages (from-to)5741-5751
Number of pages11
JournalMolecular and Cellular Biology
Issue number24
Publication statusPublished - 1 Dec 2010


  • Vertebrate Evolution, SCL Locus