Title | cis-Regulatory remodeling of the SCL locus during vertebrate evolution. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Göttgens 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 |
Journal | Mol Cell Biol |
Volume | 30 |
Issue | 24 |
Pagination | 5741-51 |
Date Published | 2010 Dec |
ISSN | 1098-5549 |
Keywords | Animals, 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 |
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. |
DOI | 10.1128/MCB.00870-10 |
Alternate Journal | Mol. Cell. Biol. |
PubMed ID | 20956563 |
PubMed Central ID | PMC3004278 |
Grant List | G0800784 / / Medical Research Council / United Kingdom / / Medical Research Council / United Kingdom |