Project description:This SuperSeries is composed of the following subset Series: GSE30537: Dissecting the retinoid-induced differentiation of F9 embryonal stem cells by integrative genomics [mRNA profiling] GSE30538: Dissecting the retinoid-induced differentiation of F9 embryonal stem cells by integrative genomics [ChIP-seq] Refer to individual Series
Project description:Chavez2009 - a core regulatory network of OCT4 in human embryonic stem cells
A core OCT4-regulated network has been identified as a test case, to analyase stem cell characteristics and cellular differentiation.
This model is described in the article:
In silico identification of a core regulatory network of OCT4 in human embryonic stem cells using an integrated approach.
Chavez L, Bais AS, Vingron M, Lehrach H, Adjaye J, Herwig R
BMC Genomics, 2009, 10:314
Abstract:
BACKGROUND: The transcription factor OCT4 is highly expressed in pluripotent embryonic stem cells which are derived from the inner cell mass of mammalian blastocysts. Pluripotency and self renewal are controlled by a transcription regulatory network governed by the transcription factors OCT4, SOX2 and NANOG. Recent studies on reprogramming somatic cells to induced pluripotent stem cells highlight OCT4 as a key regulator of pluripotency.
RESULTS: We have carried out an integrated analysis of high-throughput data (ChIP-on-chip and RNAi experiments along with promoter sequence analysis of putative target genes) and identified a core OCT4 regulatory network in human embryonic stem cells consisting of 33 target genes. Enrichment analysis with these target genes revealed that this integrative analysis increases the functional information content by factors of 1.3 - 4.7 compared to the individual studies. In order to identify potential regulatory co-factors of OCT4, we performed a de novo motif analysis. In addition to known validated OCT4 motifs we obtained binding sites similar to motifs recognized by further regulators of pluripotency and development; e.g. the heterodimer of the transcription factors C-MYC and MAX, a prerequisite for C-MYC transcriptional activity that leads to cell growth and proliferation.
CONCLUSION: Our analysis shows how heterogeneous functional information can be integrated in order to reconstruct gene regulatory networks. As a test case we identified a core OCT4-regulated network that is important for the analysis of stem cell characteristics and cellular differentiation. Functional information is largely enriched using different experimental results. The de novo motif discovery identified well-known regulators closely connected to the OCT4 network as well as potential new regulators of pluripotency and differentiation. These results provide the basis for further targeted functional studies.
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Project description:PCL family protein Phf19/Pcl3 is one of the accessory components of the PRC2 core complex, and Phf19 is highly expressed in murine ES cells and an ES cell-like embryonic carcinoma cell line, F9 cells. Here we performed microarray analysis of embryonal carcinoma cell line F9 following Phf19 knockdown by shRNA. Knocking down Phf19/Pcl3 in F9 embryonic cells led to derepression of numerous PRC2 direct target genes.
Project description:PCL family protein Phf19/Pcl3 is one of the accessory components of the PRC2 core complex, and Phf19 is highly expressed in murine ES cells and an ES cell-like embryonic carcinoma cell line, F9 cells. Here we performed microarray analysis of embryonal carcinoma cell line F9 following Phf19 knockdown by shRNA. Knocking down Phf19/Pcl3 in F9 embryonic cells led to derepression of numerous PRC2 direct target genes. 4 sampels including 2 shRNA vector control cell lines and 2 shPhf19 cell lines were used for RNA extraction and Affymetrix mouse 430 2.0 arrays.
Project description:Effect of all trans retinoic acid and the novel retinoid, ST1926, on the profile of gene expression in F9 teratocarcinoma sublines characterized by the presence or absence of the RAR gamma nuclear retinoic acid receptor