title: Functional Brachyury binding sites establish a temporal read-out of gene expression in the Ciona notochord.
abstract: The appearance of the notochord represented a milestone in Deuterostome evolution. The notochord is necessary for the development of the chordate body plan and for the formation of the vertebral column and numerous organs. It is known that the transcription factor Brachyury is required for notochord formation in all chordates, and that it controls transcription of a large number of target genes. However, studies of the structure of the cis-regulatory modules (CRMs) through which this control is exerted are complicated in vertebrates by the genomic complexity and the pan-mesodermal expression territory of Brachyury. We used the ascidian Ciona, in which the single-copy Brachyury is notochord-specific and CRMs are easily identifiable, to carry out a systematic characterization of Brachyury-downstream notochord CRMs. We found that Ciona Brachyury (Ci-Bra) controls most of its targets directly, through non-palindromic binding sites that function either synergistically or individually to activate early- and middle-onset genes, respectively, while late-onset target CRMs are controlled indirectly, via transcriptional intermediaries. These results illustrate how a transcriptional regulator can efficiently shape a shallow gene regulatory network into a multi-tiered transcriptional output, and provide insights into the mechanisms that establish temporal read-outs of gene expression in a fast-developing chordate embryo.
authors.affiliation: Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, New York, United States of America.
authors.forename: Lavanya
authors.initials: L
authors.lastname: Katikala
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Aihara
authors.forename: Yale J
authors.initials: YJ
authors.lastname: Passamaneck
authors.forename: Stefan
authors.initials: S
authors.lastname: Gazdoiu
authors.forename: Diana S
authors.initials: DS
authors.lastname: José-Edwards
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Kugler
authors.forename: Izumi
authors.initials: I
authors.lastname: Oda-Ishii
authors.forename: Janice H
authors.initials: JH
authors.lastname: Imai
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nibu
authors.forename: Anna
authors.initials: A
authors.lastname: Di Gregorio
mesh_terms: D000818:Animals; D001665:Binding Sites; D002938:Ciona intestinalis / Q000235:genetics* / Q000254:growth & development; D016384:Consensus Sequence / Q000235:genetics; D005326:Fetal Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D009672:Notochord / Q000254:growth & development / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D015203:Reproducibility of Results; D013045:Species Specificity; D020825:T-Box Domain Proteins / Q000378:metabolism*; D013997:Time Factors; D000098908:Brachyury Protein
chemical_list: D005326:Fetal Proteins; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein