Brachyury, Foxa2 and the cis-Regulatory Origins of the Notochord

Diana S. José-Edwards, Izumi Oda-Ishii, Jamie E. Kugler, Yale J. Passamaneck, Lavanya Katikala, Yutaka Nibu, Anna Di Gregorio

Research output: Contribution to journalArticle

Abstract

A main challenge of modern biology is to understand how specific constellations of genes are activated to differentiate cells and give rise to distinct tissues. This study focuses on elucidating how gene expression is initiated in the notochord, an axial structure that provides support and patterning signals to embryos of humans and all other chordates. Although numerous notochord genes have been identified, the regulatory DNAs that orchestrate development and propel evolution of this structure by eliciting notochord gene expression remain mostly uncharted, and the information on their configuration and recurrence is still quite fragmentary. Here we used the simple chordate Ciona for a systematic analysis of notochord cis-regulatory modules (CRMs), and investigated their composition, architectural constraints, predictive ability and evolutionary conservation. We found that most Ciona notochord CRMs relied upon variable combinations of binding sites for the transcription factors Brachyury and/or Foxa2, which can act either synergistically or independently from one another. Notably, one of these CRMs contains a Brachyury binding site juxtaposed to an (AC) microsatellite, an unusual arrangement also found in Brachyury-bound regulatory regions in mouse. In contrast, different subsets of CRMs relied upon binding sites for transcription factors of widely diverse families. Surprisingly, we found that neither intra-genomic nor interspecific conservation of binding sites were reliably predictive hallmarks of notochord CRMs. We propose that rather than obeying a rigid sequence-based cis-regulatory code, most notochord CRMs are rather unique. Yet, this study uncovered essential elements recurrently used by divergent chordates as basic building blocks for notochord CRMs.

Original languageEnglish (US)
Article numbere1005730
JournalPLoS Genetics
Volume11
Issue number12
DOIs
StatePublished - 2015

Fingerprint

Notochord
Chordata
binding sites
gene expression
transcription factors
gene
Binding Sites
embryo
genomics
DNA
embryo (animal)
Transcription Factors
genes
microsatellite repeats
Gene Expression
Biological Sciences
Brachyury protein
chordate
Nucleic Acid Regulatory Sequences
mice

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

José-Edwards, D. S., Oda-Ishii, I., Kugler, J. E., Passamaneck, Y. J., Katikala, L., Nibu, Y., & Di Gregorio, A. (2015). Brachyury, Foxa2 and the cis-Regulatory Origins of the Notochord. PLoS Genetics, 11(12), [e1005730]. https://doi.org/10.1371/journal.pgen.1005730

Brachyury, Foxa2 and the cis-Regulatory Origins of the Notochord. / José-Edwards, Diana S.; Oda-Ishii, Izumi; Kugler, Jamie E.; Passamaneck, Yale J.; Katikala, Lavanya; Nibu, Yutaka; Di Gregorio, Anna.

In: PLoS Genetics, Vol. 11, No. 12, e1005730, 2015.

Research output: Contribution to journalArticle

José-Edwards, DS, Oda-Ishii, I, Kugler, JE, Passamaneck, YJ, Katikala, L, Nibu, Y & Di Gregorio, A 2015, 'Brachyury, Foxa2 and the cis-Regulatory Origins of the Notochord', PLoS Genetics, vol. 11, no. 12, e1005730. https://doi.org/10.1371/journal.pgen.1005730
José-Edwards DS, Oda-Ishii I, Kugler JE, Passamaneck YJ, Katikala L, Nibu Y et al. Brachyury, Foxa2 and the cis-Regulatory Origins of the Notochord. PLoS Genetics. 2015;11(12). e1005730. https://doi.org/10.1371/journal.pgen.1005730
José-Edwards, Diana S. ; Oda-Ishii, Izumi ; Kugler, Jamie E. ; Passamaneck, Yale J. ; Katikala, Lavanya ; Nibu, Yutaka ; Di Gregorio, Anna. / Brachyury, Foxa2 and the cis-Regulatory Origins of the Notochord. In: PLoS Genetics. 2015 ; Vol. 11, No. 12.
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