PUBLICATION

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

Authors

Chan, T.M., Chao, C.H., Wang, H.D., Yu, Y.J., and Yuh, C.H.

ID

ZDB-PUB-081218-30

Date

2009

Source

Developmental Biology 326(2): 456-470 (Journal)

Registered Authors

Yuh, Chiou-Hwa (Cathy)

Keywords

sox17, sox32, pou5f1, transcription regulation, evolutionarily conserved non-coding region, zebrafish endoderm development, Gene Regulatory Networks (GRNs)

MeSH Terms

Recombinant Fusion Proteins/genetics
Recombinant Fusion Proteins/metabolism
SOX Transcription Factors/genetics
SOX Transcription Factors/metabolism
Evolution, Molecular*
DNA Mutational Analysis
Animals
Octamer Transcription Factor-3/genetics
Octamer Transcription Factor-3/metabolism
Base Sequence
Humans
Zebrafish Proteins*/genetics
Zebrafish Proteins*/metabolism
Sequence Alignment
Gene Expression Regulation, Developmental*
Signal Transduction/physiology
Endoderm/physiology
Regulatory Sequences, Nucleic Acid*
Mutagenesis, Site-Directed
Molecular Sequence Data
Gene Regulatory Networks
SOXF Transcription Factors*/genetics
SOXF Transcription Factors*/metabolism
Zebrafish*/genetics
Zebrafish*/metabolism
Protein Binding

(all 26)

PubMed

19084513 Full text @ Dev. Biol.

Abstract

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

Figures