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In silico identification of a core regulatory network of OCT4 in human embryonic stem cells using an integrated approach.
BMC Genomics. 2009 Jul 15; 10:314.BG

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.

Authors+Show Affiliations

Department of Vertebrate Genomics, Max-Planck-Institute for Molecular Genetics, Berlin, Germany. chavez@molgen.mpg.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19604364

Citation

Chavez, Lukas, et al. "In Silico Identification of a Core Regulatory Network of OCT4 in Human Embryonic Stem Cells Using an Integrated Approach." BMC Genomics, vol. 10, 2009, p. 314.
Chavez L, Bais AS, Vingron M, et al. In silico identification of a core regulatory network of OCT4 in human embryonic stem cells using an integrated approach. BMC Genomics. 2009;10:314.
Chavez, L., Bais, A. S., Vingron, M., Lehrach, H., Adjaye, J., & Herwig, R. (2009). In silico identification of a core regulatory network of OCT4 in human embryonic stem cells using an integrated approach. BMC Genomics, 10, 314. https://doi.org/10.1186/1471-2164-10-314
Chavez L, et al. In Silico Identification of a Core Regulatory Network of OCT4 in Human Embryonic Stem Cells Using an Integrated Approach. BMC Genomics. 2009 Jul 15;10:314. PubMed PMID: 19604364.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In silico identification of a core regulatory network of OCT4 in human embryonic stem cells using an integrated approach. AU - Chavez,Lukas, AU - Bais,Abha S, AU - Vingron,Martin, AU - Lehrach,Hans, AU - Adjaye,James, AU - Herwig,Ralf, Y1 - 2009/07/15/ PY - 2009/01/13/received PY - 2009/07/15/accepted PY - 2009/7/17/entrez PY - 2009/7/17/pubmed PY - 2009/8/6/medline SP - 314 EP - 314 JF - BMC genomics JO - BMC Genomics VL - 10 N2 - 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. SN - 1471-2164 UR - https://www.unboundmedicine.com/medline/citation/19604364/In_silico_identification_of_a_core_regulatory_network_of_OCT4_in_human_embryonic_stem_cells_using_an_integrated_approach_ L2 - https://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-10-314 DB - PRIME DP - Unbound Medicine ER -