cis-Regulatory remodeling of the SCL locus during vertebrate evolution.
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.
Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
Berthold
B
Göttgens
Rita
R
Ferreira
Maria-José
MJ
Sanchez
Shoko
S
Ishibashi
Juan
J
Li
Dominik
D
Spensberger
Pascal
P
Lefevre
Katrin
K
Ottersbach
Michael
M
Chapman
Sarah
S
Kinston
Kathy
K
Knezevic
Maarten
M
Hoogenkamp
George A
GA
Follows
Constanze
C
Bonifer
Enrique
E
Amaya
Anthony R
AR
Green
D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D005075:Biological Evolution; D002645:Chickens; D017124:Conserved Sequence / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D016415:Sequence Alignment; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014714:Vertebrates / Q000235:genetics*; D029867:Xenopus Proteins / Q000235:genetics* / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; D029867:Xenopus Proteins; C489365:TAL1 protein, Xenopus; C489366:Tal1 protein, mouse; C067143:TAL1 protein, human