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Mol Cell Biol. December 1, 2010; 30 (24): 5741-51.

cis-Regulatory remodeling of the SCL locus during vertebrate evolution.

Göttgens B , Ferreira R , Sanchez MJ , Ishibashi S , Li J , Spensberger D , Lefevre P , Ottersbach K , Chapman M , Kinston S , Knezevic K , Hoogenkamp M , Follows GA , Bonifer C , Amaya E , Green AR .

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.

PubMed ID: 20956563
PMC ID: PMC3004278
Article link: Mol Cell Biol.
Grant support: Medical Research Council , G0800784 Medical Research Council , G0900729/1 National Centre for the Replacement, Refinement and Reduction of Animals in Research, MRC_G0800784 Medical Research Council , NC3RS_G0900729/1 National Centre for the Replacement, Refinement and Reduction of Animals in Research

Genes referenced: tal1

External Resources:

Anand, 2003, Pubmed[+]

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