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
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