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

Titlecis-Regulatory remodeling of the SCL locus during vertebrate evolution.
Publication TypeJournal Article
Year of Publication2010
AuthorsGöttgens B, Ferreira R, Sanchez M-J, 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
JournalMol Cell Biol
Date Published2010 Dec
KeywordsAnimals, Base Sequence, Basic Helix-Loop-Helix Transcription Factors, Biological Evolution, Chickens, Conserved Sequence, DNA-Binding Proteins, Embryo, Mammalian, Embryo, Nonmammalian, Gene Expression Regulation, Developmental, Genes, Reporter, Hematopoiesis, Humans, Mice, Mice, Transgenic, Molecular Sequence Data, Proto-Oncogene Proteins, Regulatory Sequences, Nucleic Acid, Sequence Alignment, Tissue Distribution, Transcription Factors, Vertebrates, Xenopus Proteins

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.

Alternate JournalMol. Cell. Biol.
PubMed ID20956563
PubMed Central IDPMC3004278
Grant ListG0800784 / / Medical Research Council / United Kingdom
/ / Medical Research Council / United Kingdom
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