Functional analysis of the evolutionarily conserved Cis-regulatory elements on the Sox17 gene in zebrafish

Chan, T.M., Chao, C.H., Wang, H.D., Yu, Y.J., and Yuh, C.H.
Developmental Biology   326(2): 456-470 (Journal)
Registered Authors
Yuh, Chiou-Hwa (Cathy)
sox17, sox32, pou5f1, transcription regulation, evolutionarily conserved non-coding region, zebrafish endoderm development, Gene Regulatory Networks (GRNs)
MeSH Terms
  • Animals
  • Base Sequence
  • DNA Mutational Analysis
  • Endoderm/physiology
  • Evolution, Molecular*
  • Gene Expression Regulation, Developmental*
  • Gene Regulatory Networks
  • Humans
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Octamer Transcription Factor-3/genetics
  • Octamer Transcription Factor-3/metabolism
  • Protein Binding
  • Recombinant Fusion Proteins/genetics
  • Recombinant Fusion Proteins/metabolism
  • Regulatory Sequences, Nucleic Acid*
  • SOX Transcription Factors/genetics
  • SOX Transcription Factors/metabolism
  • SOXF Transcription Factors*/genetics
  • SOXF Transcription Factors*/metabolism
  • Sequence Alignment
  • Signal Transduction/physiology
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
19084513 Full text @ Dev. Biol.
The Sox17 is an important transcription factor for endodermal cells (Danio rerio). According to the predictions of the GRNs, based on perturbation experiments and literature search, the sox17 gene is engaged with two other regulatory genes, sox32 and pou5f1. Nodal signaling operated on several endoderm-specific transcription factors to determine the endoderm specification. In addition, endoderm specification requires the Fgf and Bmp signaling pathways to be repressed in the cells which will become endoderm. It is predicted that Nodal activates sox32 and works synergistically with Pou5f1 to activate sox17. Bmp represses the expression of sox17 on the ventral side and Fgf represses it on the dorsal side. The regulatory inputs of sox17 at the genomic sequence level are not known. Here, we have uncovered the relevant sox17 cis-regulatory elements, and examined the specific input predictions of the GRNs. We discovered three conserved modules, A, B, and C, with a synergistic effect among them. We revealed that the Pou5f1-binding element on the B module and the Sox32-binding element on the C module work synergistically. Furthermore, an evolutionarily non-conserved R module exhibits a repressive effect on both the ventral and dorsal side. We have directly demonstrated the structural and functional relationships of the genomic code at this key node of the endoderm GRNs in zebrafish development. This information provides new insight into the complexity of endoderm formation and serves as a valuable resource for the establishment of a complete endoderm gene regulatory network.
Genes / Markers
Figure Gallery
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes