Please use this identifier to cite or link to this item:
https://doi.org/10.1371/journal.pgen.1003852
Title: | Genome Wide Analysis Reveals Zic3 Interaction with Distal Regulatory Elements of Stage Specific Developmental Genes in Zebrafish | Authors: | Winata C.L. Kondrychyn I. Kumar V. Srinivasan K.G. Orlov Y. Ravishankar A. Prabhakar S. Stanton L.W. Korzh V. Mathavan S. |
Keywords: | membrane protein protein Nodal protein Zic3 transforming growth factor beta unclassified drug homeodomain protein transcription factor zebrafish protein zic3 protein, zebrafish amino acid sequence animal tissue article binding site chromatin immunoprecipitation controlled study down regulation embryo gastrulation gene expression profiling genetic transcription in vivo study intron microarray analysis molecular evolution morphogenesis nonhuman protein analysis protein binding protein expression protein function protein localization protein motif sequence analysis signal transduction upregulation Wnt signaling pathway zebra fish animal gene expression regulation genetics genomics growth, development and aging metabolism regulatory sequence Animals Binding Sites Body Patterning Gene Expression Regulation, Developmental Genomics Homeodomain Proteins Regulatory Elements, Transcriptional Regulatory Sequences, Nucleic Acid Transcription Factors Wnt Signaling Pathway Zebrafish Zebrafish Proteins |
Issue Date: | 2013 | Citation: | Winata C.L., Kondrychyn I., Kumar V., Srinivasan K.G., Orlov Y., Ravishankar A., Prabhakar S., Stanton L.W., Korzh V., Mathavan S. (2013). Genome Wide Analysis Reveals Zic3 Interaction with Distal Regulatory Elements of Stage Specific Developmental Genes in Zebrafish. PLoS Genetics 9 (10) : e1003852. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pgen.1003852 | Rights: | Attribution 4.0 International | Abstract: | Zic3 regulates early embryonic patterning in vertebrates. Loss of Zic3 function is known to disrupt gastrulation, left-right patterning, and neurogenesis. However, molecular events downstream of this transcription factor are poorly characterized. Here we use the zebrafish as a model to study the developmental role of Zic3 in vivo, by applying a combination of two powerful genomics approaches - ChIP-seq and microarray. Besides confirming direct regulation of previously implicated Zic3 targets of the Nodal and canonical Wnt pathways, analysis of gastrula stage embryos uncovered a number of novel candidate target genes, among which were members of the non-canonical Wnt pathway and the neural pre-pattern genes. A similar analysis in zic3-expressing cells obtained by FACS at segmentation stage revealed a dramatic shift in Zic3 binding site locations and identified an entirely distinct set of target genes associated with later developmental functions such as neural development. We demonstrate cis-regulation of several of these target genes by Zic3 using in vivo enhancer assay. Analysis of Zic3 binding sites revealed a distribution biased towards distal intergenic regions, indicative of a long distance regulatory mechanism; some of these binding sites are highly conserved during evolution and act as functional enhancers. This demonstrated that Zic3 regulation of developmental genes is achieved predominantly through long distance regulatory mechanism and revealed that developmental transitions could be accompanied by dramatic changes in regulatory landscape. © 2013 Winata et al. | Source Title: | PLoS Genetics | URI: | https://scholarbank.nus.edu.sg/handle/10635/161617 | ISSN: | 15537390 | DOI: | 10.1371/journal.pgen.1003852 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
Show full item record
Files in This Item:
File | Description | Size | Format | Access Settings | Version | |
---|---|---|---|---|---|---|
10_1371_journal_pgen_1003852.pdf | 6.42 MB | Adobe PDF | OPEN | None | View/Download |
This item is licensed under a Creative Commons License