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PLURIPOTENCY REGULATOR ZIC3 IS AN EARLY LINEAGE SPECIFIER

ABSTRACT: Sustained expression of the key pluripotency transcriptional regulators and proliferative factors is needed for the maintenance of embryonic stem cells and early progenitors of various lineages. Zic3 is one of those factors which has been shown to be important for embryonic stem cell pluripotency. Through combinatorial analysis of transcription factor binding sites and the corresponding gene-regulation, we show that Zic3 not only activates key pluripotency genes but also acts cooperatively with them in connecting important circuits of regulation in ES cell in proliferation and maintenance of early progenitors.

ORGANISM(S): Mus musculus

PROVIDER: GSE37889 | GEO | 2015/12/30

SECONDARY ACCESSION(S): PRJNA165125

REPOSITORIES: GEO

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Zic3 ChIP-on-chip in mouse ES cells

2010-09-13 | GSE22195 | GEO

Zic3 ChIP-on-chip in mouse ES cells

Project description:The transcription factor Zic3 is required for maintenance of embryonic stem (ES) cell pluripotency (Lim LS et al, Mol Biol Cell. 2007;18:1348-1358). By genome-wide chromatin immunoprecipitation (ChIP-chip) in ES cells, we have identified 379 direct Zic3 targets, many of which are functionally associated with pluripotency, cell cycle, proliferation, oncogenesis and early embryogenesis. E14 cells were cultured to a density of 1 x 108 cells for each IP. Two biological replicates were performed per experiment. Cells were cross-linked for 10 minutes at room temperature with 1% (w/v) formaldehyde and the reaction subsequently quenched with 125mM glycine. Nuclear fractions were isolated and the DNA sheared to average lengths of 200-500 bp. For analysis on mouse promoter arrays, purified ChIP material was processed according to the Agilent ChIP-on-chip protocol, and labeled DNA was hybridized to Agilent mouse promoter ChIP-on-chip arrays for 40 hours at 65oC (G4490A; Agilent Technologies, Santa Clara, CA). Chips were washed and scanned as per manufacturer’s protocol and the results were processed with Agilent's ChIP Analytics software v1.3. A p-value cutoff <0.001 was specified in our analysis. To further minimize false positives, we applied a “neighborhood voting” algorithm [2] to filter for high confidence Zic3-enriched sites, wherein binding was considered genuine only in the presence of a second, significantly enriched, neighboring probe (p < 0.005).

2010-09-13 | E-GEOD-22195 | biostudies-arrayexpress

ZIC2 and ZIC3 promote SWI/SNF recruitment to safeguard progression towards human primed pluripotency [ATAC-Seq]

Project description:ZIC2 and ZIC3 are essential for acquisition and maintenance of primed pluripotency. In this study, we conducted ATAC-seq in single and compound knockout of ZIC2, ZIC3 and ZIC5 primed hESCs, naïve hESCs lacking ZIC3 that inducibly express ZIC2, naive hESCs that inducible express ZIC2 or ZIC3, ZIC3-depleted primed hESCs that were cultured in 5iLAF medium for six days and undergoing reversion to a naive state, naive hESCs expressing ectopic ZIC2 in the presence of a BRG1 PROTAC.

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ZIC2 and ZIC3 promote SWI/SNF recruitment to safeguard progression towards human primed pluripotency [RNA-seq]

Project description:ZIC2 and ZIC3 are essential for acquisition and maintenance of primed pluripotency. In this study, we conducted next generation sequencing of polyA-enriched bulk RNA in single and compound knockouts of ZIC2, ZIC3 and ZIC5 primed hESCs, naïve hESCs lacking ZIC3 that inducibly express ZIC2, and primed hESCs that were cultured in 5iLAF medium for six days and undergoing reversion to a naive state.

2024-08-20 | GSE270786 | GEO

ZIC2 and ZIC3 promote SWI/SNF recruitment to safeguard progression towards human primed pluripotency [CUT&Tag]

Project description:ZIC2 and ZIC3 are essential for acquisition and maintenance of primed pluripotency. In this study, we profiled chromatin occupancy of BRG1, EZH2, H3K27ac and H3K4me3 upon concomitant loss of ZIC2 and ZIC3 in primed hESCs, and of BRG1 upon ectopic expression of ZIC2 for increasing periods of time in naïve hESCs.

2024-08-20 | GSE270822 | GEO

Zic3 interacts with distant regulatory elements to regulate zebrafish developmental genes

Project description:Zic3 regulates early embryonic patterning in vertebrates. Its loss-of-function disrupts gastrulation, left-right patterning, and neurogenesis. We use the zebrafish as a model to study the developmental role of Zic3 in vivo. Using a combination of two genomics approaches – ChIP-seq and microarray, we identified Zic3 targets, which include genes from the Nodal and Wnt pathways, and show for the first time cis-regulation of these genes by Zic3 using in vivo enhancer assay. We uncovered a previously unrecognized link between Zic3 and the non-canonical Wnt pathway in gastrulation and left-right patterning, and identified neural pre-pattern genes as Zic3 targets during the early steps of neural induction. Zic3 preferably binds to distal intergenic regions, some of which contain evolutionarily conserved functional enhancers. Our study establishes the zebrafish as an excellent model for genome-wide study of a transcription factor in vivo.

2014-02-27 | GSE41458 | GEO

Zic3 interacts with distant regulatory elements to regulate zebrafish developmental genes

2014-02-27 | E-GEOD-41458 | biostudies-arrayexpress

ZIC2 and ZIC3 promote SWI/SNF recruitment to safeguard progression towards human primed pluripotency [ChIP-seq]

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2024-08-20 | GSE270784 | GEO

Whole heart transcriptional response to complete and epiblast-specfic deletion of Zic3 in 15.5 dpc mouse embryos

Project description:In order to better understand the molecular basis for the heart defects seen in Zic3 null and epiblast CKO embryos, we investigated whether complete or epiblast-specific deletion of Zic3 would impact later embryonic heart development at the transcriptional level by whole genome expression microarray.

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Genome-wide analysis of transcription factor binding sites during somatic cell reprogramming

Project description:We report that Zic3 and Esrrb synergistically enhance the reprogramming efficiency when transduced with Oct4, Sox2 and Klf4 (OSK) into murine fibroblasts. By ChIP-seq analysis, we reveal that Zic3 recruits Esrrb to its own binding sites, some of which are proximal to glycolysis-related genes, thereby cooperatively upregulating these genes to activate glycolytic metabolism, and that Esrrb binds to genes related to mitochondrial oxidative phosphorylation. Therefore, our study suggests that Zic3 and Esrrb activate pluripotency gene network by regulating the balance of metabolic pathways.

2017-05-02 | GSE89155 | GEO

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