cis-Regulatory Remodeling of the SCL Locus during Vertebrate Evolution

Berthold Goettgens, Rita Ferreira, Maria-Jose Sanchez, Shoko Ishibashi, Juan Li, Dominik Spensberger, Pascal Lefevre, Katrin Ottersbach, Michael Chapman, Sarah Kinston, Kathy Knezevic, Maarten Hoogenkamp, George A. Follows, Constanze Bonifer, Enrique Amaya, Anthony R. Green*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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
Volume30
Issue number24
DOIs
Publication statusPublished - Dec 2010

Keywords

  • STEM-CELL ENHANCER
  • MORPHOLOGICAL EVOLUTION
  • TRANSCRIPTIONAL REGULATION
  • DEFINITIVE HEMATOPOIESIS
  • ENDOTHELIAL DEVELOPMENT
  • DEVELOPING BRAIN
  • XENOPUS EMBRYOS
  • LYSOZYME LOCUS
  • GATA FACTORS
  • IN-VIVO

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