Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA106613 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:SALL4 ChIP-chip using NimbleGen HG18 RefSeq Promoter tiling array (2.7kb)
| PRJNA107507 | ENA
Project description:Increasing studies suggest that SALL4 may play vital roles in leukemogenesis. We have used chromatin immunoprecipitation followed by microarray hybridization as a screening tool to determine potential genes that may account for the role SALL4 plays in leukemogenesis. Analysis of SALL4 binding sites reveals that genes involved in cell death, cancer, DNA replication/repair, and cell cycle were highly enriched (p<0.05). These genes include 38 important apoptosis-inducing genes (TNF, TP53, PTEN, CARD9, CARD11, CYCS, LTA) and apoptosis-inhibiting genes (Bmi-1, BCL2, XIAP, DAD1, TEGT). Real-time PCR has shown that expression levels of these genes changed significantly after SALL4 knockdown, which ubiquitously led to cell apoptosis. Flow cytometry revealed that reduction of SALL4 expression in NB4 and other leukemia cell lines dramatically increased caspase-3, Annexin V, and DNA fragmentation activity. Bromodeoxyuridine-incorporation assays showed decreased numbers of S phase cells and increased numbers of G1- and G2- phase cells indicating reduced DNA synthesis, consistent with results from cell proliferation assays. In addition, NB4 cells that express low levels of SALL4 have significantly decreased tumorigenecity in immunodeficient mice. Our studies provide a foundation in the development of leukemia stem cell-specific therapy by targeting SALL4. Keywords: ChIP-chip The global targets of SALL4 were determined using a NimbleGen promoter tiling array (2.7kb, information below) in the human cell line NB4. Because SALL4 is thought to play a significant role in leukemogenesis we focused primarily on genes involved in apoptosis and only used the ChIP-chip array as a screening tool to identify potential genes that may bind these genes. Upon identification and verification of apoptosis genes bound by SALL4 we utilized functional assays to determine the effect of SALL4 on these genes. In addition, gene expression profiling was used to determine pathways functionally altered by Sall4 reduction. Source: UCSC Build: HG18 Probe Length: 50-75mer Median Probe Spacing: 100bp Probes per Array: 385,000 Feature Size: 16μm x 16μm Array Dimensions: 17.4mm x 13mm Overall Slide Dimensions: 1" x 3" (25 x 75mm) Recommended Storage: Store arrays desiccated at room temperature. Promoter tiling from 2200bp upstream and 500bp downstream of the transcription start site for RefSeq genes.
2008-05-17 | E-GEOD-10734 | biostudies-arrayexpress
Project description:DNA methylation is extensively reprogrammed during early phases of mammalian development yet individual genomic targets of this process are largely unknown. We optimized MeDIP (Methylated DNA Immunoprecipitation) for low numbers of cells and profiled DNA methylation genome-wide during early development of the mouse embryonic lineage in vivo. We mapped DNA methylation at 3 consecutive stages of early development: E3.5 blastocysts, E6.5 epiblasts and E9.5 whole embryos. MeDIP and Input samples were hybridized to Nimblegen HD2 MM8 promoter deluxe arrays covering 12 kb of all gene promoters. Experiments were performed in duplicates for E3.5 blastocysts and triplicates for E6.5 epibalsts and E9.5 embryos. As a control we also hybridized pooled unamplified MeDIPs from E9.5 to Nimblegen 385K MM8 RefSeq promoter arrays.
2010-11-01 | E-GEOD-22831 | biostudies-arrayexpress
Project description:Embryonic stem cells have potential utility in regenerative medicine due to their pluripotent characteristics. Sall4, a zinc-finger transcription factor, is expressed very early in embryonic development with Oct4 and Nanog, two well characterized pluripotency regulators. Sall4 plays an important role in governing the fate of stem cells through transcriptional regulation of both Oct4 and Nanog. Using chromatin immunoprecipitation coupled to microarray hybridization (ChIP on Chip), we have mapped global gene targets of Sall4 unveiling possible regulation of broad ES cell functions. Approximately 5,000 genes were identified that were bound by the Sall4 protein and many of these have major functions in developmental and regulatory pathways. Sall4 bound more than six times as many annotated genes within promoter regions as Oct4 and twice as many as Nanog. Immunoprecipitation revealed a heterotrimeric protein complex between Sall4, Oct4, and Nanog, consistent with binding site co-occupancies. Further, Sall4 bound many genes that are regulated in part by the chromatin-based epigenetic events mediated by polycomb-repressive complexes and bivalent domains. This suggests that Sall4 plays a central and diverse role in regulating stem cell pluripotency during early embryonic development that involves integration of transcriptional and epigenetic control processes. Keywords: ChIP-chip We used ChIP-chip to map global promoter bound by Sall4, a zinc finger transcription factor. Growing evidence has suggested that Sall4 plays a vital role in ES cell pluripotency maintenance. Evidence for this includes its recent use as a marker for somatic cell reprogramming, in a genetic signature for ES cells, and evidence that Sall4 enhances reprogramming. These recent findings and two previously described interactions with Oct4 and Nanog strongly support the role of Sall4 in ES cells. This hypothesis was furthered here as we show that Sall4 plays important roles through transcriptional regulation of vital ES cell genes.
2008-09-01 | E-GEOD-11305 | biostudies-arrayexpress
Project description:A small number of transcription factors, including Oct-3/4 and Sox2, constitute the transcriptional network that maintains pluripotency in embryonic stem (ES) cells. Previous reports suggested that some of these factors form a complex that binds the Oct-Sox element, a composite sequence consisting of closely juxtaposed Oct-3/4-binding and Sox2-binding sites. However, little is known regarding the components of the complex. In this study, we show that Sall4, a member of the Spalt-like family of proteins, directly interacts with Sox2 and Oct-3/4. Sall4 in combination with Sox2 or Oct-3/4 simultaneously occupies the Oct-Sox elements in mouse ES cells. Sall4 knockdown led to differentiation of ES cells. Overexpression of Sall4 in ES cells increased reporter activities in a luciferase assay when the Pou5f1- or Nanog-derived Oct-Sox element was included in the reporter. Microarray analyses revealed that Sall4 and Sox2 bound to the same genes in ES cells significantly more frequently than expected from random coincidence. These factors appeared to bind the promoter regions of a subset of the Sall4- and Sox2-double-positive genes in precisely similar distribution patterns along the promoter regions, suggesting that Sall4 and Sox2 associate with such Sall4/Sox2-overlapping genes as a complex. Importantly, gene ontology analyses indicated that the Sall4/Sox2-overlapping gene set is enriched for genes involved in maintaining pluripotency. Sall4/Sox2/Oct-3/4-triple-positive genes identified by referring to a previous study identifying Oct-3/4-bound genes in ES cells were further enriched for pluripotency genes than Sall4/Sox2-double-positive genes. These results demonstrate that Sall4 contributes to the transcriptional network operating in pluripotent cells, together with Oct-3/4 and Sox2. ChIP-on-chip experiments using anti-Sall4 or anti-Sox2 antibody were performed.
2012-12-28 | E-GEOD-40072 | biostudies-arrayexpress
Project description:In order to determine the cell potency, by identification of genes responsible for pluri/multi potency, we performed a global gene expression profiling of MDSC isolated from five week old male wild type(WT), C57Bl6J and another hypertrophied musculature mouse genotype called myostatin null (Mstn-/-) mice using microarray analysis and compared this gene expression to that of a standard mouse ES cell line W4. Muscle derived stem cells (MDSC) were isolated from WT and Mstn null mice using an established preplate technique and compared with the gene expression signature of standard mouse ES cell line W4
2012-08-01 | GSE39765 | GEO
Project description:A small number of transcription factors, including Oct-3/4 and Sox2, constitute the transcriptional network that maintains pluripotency in embryonic stem (ES) cells. Previous reports suggested that some of these factors form a complex that binds the Oct-Sox element, a composite sequence consisting of closely juxtaposed Oct-3/4-binding and Sox2-binding sites. However, little is known regarding the components of the complex. In this study, we show that Sall4, a member of the Spalt-like family of proteins, directly interacts with Sox2 and Oct-3/4. Sall4 in combination with Sox2 or Oct-3/4 simultaneously occupies the Oct-Sox elements in mouse ES cells. Sall4 knockdown led to differentiation of ES cells. Overexpression of Sall4 in ES cells increased reporter activities in a luciferase assay when the Pou5f1- or Nanog-derived Oct-Sox element was included in the reporter. Microarray analyses revealed that Sall4 and Sox2 bound to the same genes in ES cells significantly more frequently than expected from random coincidence. These factors appeared to bind the promoter regions of a subset of the Sall4- and Sox2-double-positive genes in precisely similar distribution patterns along the promoter regions, suggesting that Sall4 and Sox2 associate with such Sall4/Sox2-overlapping genes as a complex. Importantly, gene ontology analyses indicated that the Sall4/Sox2-overlapping gene set is enriched for genes involved in maintaining pluripotency. Sall4/Sox2/Oct-3/4-triple-positive genes identified by referring to a previous study identifying Oct-3/4-bound genes in ES cells were further enriched for pluripotency genes than Sall4/Sox2-double-positive genes. These results demonstrate that Sall4 contributes to the transcriptional network operating in pluripotent cells, together with Oct-3/4 and Sox2.
2012-12-28 | GSE40072 | GEO
Project description:Sall4 is a transcription factor essential for early mammalian development. Though it is reported to play an important role in embryonic stem (ES) cell self-renewal, whether it is an essential pluripotency factor has been disputed. Though Sall4 is known to associate with the Nucleosome Remodeling and Deacetylase (NuRD) complex, the nature of this interaction is unclear as NuRD and Sall4 serve opposing functions in ES cells. Here we use defined culture conditions and single-cell gene expression analyses to show that Sall4 prevents activation of the neural gene expression programme in ES cells but is dispensable for maintaining the pluripotency gene regulatory network. We further show using genome-wide analyses that while Sall4 interacts with NuRD, it neither recruits NuRD to chromatin nor influences transcription via NuRD. Rather we propose a model where, by titrating Sall4 protein, NuRD limits the differentiation-inhibiting activity of Sall4 in ES cells to enable lineage commitment.
2016-08-02 | PXD003614 | Pride
Project description:Embryonic stem cells have potential utility in regenerative medicine due to their pluripotent characteristics. Sall4, a zinc-finger transcription factor, is expressed very early in embryonic development with Oct4 and Nanog, two well characterized pluripotency regulators. Sall4 plays an important role in governing the fate of stem cells through transcriptional regulation of both Oct4 and Nanog. Using chromatin immunoprecipitation coupled to microarray hybridization (ChIP on Chip), we have mapped global gene targets of Sall4 unveiling possible regulation of broad ES cell functions. Approximately 5,000 genes were identified that were bound by the Sall4 protein and many of these have major functions in developmental and regulatory pathways. Sall4 bound more than six times as many annotated genes within promoter regions as Oct4 and twice as many as Nanog. Immunoprecipitation revealed a heterotrimeric protein complex between Sall4, Oct4, and Nanog, consistent with binding site co-occupancies. Further, Sall4 bound many genes that are regulated in part by the chromatin-based epigenetic events mediated by polycomb-repressive complexes and bivalent domains. This suggests that Sall4 plays a central and diverse role in regulating stem cell pluripotency during early embryonic development that involves integration of transcriptional and epigenetic control processes. Keywords: ChIP-chip
2008-09-01 | GSE11305 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE21054: Differential roles of Sall4 isoforms in ES cell pluripotency: expression GSE21055: Differential Role of Sall4 isoforms in ES cell pluripotency: ChIP-chip Refer to individual Series
2010-09-13 | E-GEOD-21056 | biostudies-arrayexpress