A data integration approach to mapping OCT4 gene regulatory networks operative in embryonic stem cells and embryonal carcinoma cells.

It is essential to understand the network of transcription factors controlling self-renewal of human embryonic stem cells (ESCs) and human embryonal carcinoma cells (ECs) if we are to exploit these cells in regenerative medicine regimes. Correlating gene expression levels after RNAi-based ablation o...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Marc Jung, Hedi Peterson, Lukas Chavez, Pascal Kahlem, Hans Lehrach, Jaak Vilo, James Adjaye
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/890cfceae9924bf3bc0cb21af66d9b3d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:890cfceae9924bf3bc0cb21af66d9b3d
record_format	dspace
spelling	oai:doaj.org-article:890cfceae9924bf3bc0cb21af66d9b3d2021-12-02T20:21:29ZA data integration approach to mapping OCT4 gene regulatory networks operative in embryonic stem cells and embryonal carcinoma cells.1932-620310.1371/journal.pone.0010709https://doaj.org/article/890cfceae9924bf3bc0cb21af66d9b3d2010-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20505756/?tool=EBIhttps://doaj.org/toc/1932-6203It is essential to understand the network of transcription factors controlling self-renewal of human embryonic stem cells (ESCs) and human embryonal carcinoma cells (ECs) if we are to exploit these cells in regenerative medicine regimes. Correlating gene expression levels after RNAi-based ablation of OCT4 function with its downstream targets enables a better prediction of motif-specific driven expression modules pertinent for self-renewal and differentiation of embryonic stem cells and induced pluripotent stem cells.We initially identified putative direct downstream targets of OCT4 by employing CHIP-on-chip analysis. A comparison of three peak analysis programs revealed a refined list of OCT4 targets in the human EC cell line NCCIT, this list was then compared to previously published OCT4 CHIP-on-chip datasets derived from both ES and EC cells. We have verified an enriched POU-motif, discovered by a de novo approach, thus enabling us to define six distinct modules of OCT4 binding and regulation of its target genes.A selection of these targets has been validated, like NANOG, which harbours the evolutionarily conserved OCT4-SOX2 binding motif within its proximal promoter. Other validated targets, which do not harbour the classical HMG motif are USP44 and GADD45G, a key regulator of the cell cycle. Over-expression of GADD45G in NCCIT cells resulted in an enrichment and up-regulation of genes associated with the cell cycle (CDKN1B, CDKN1C, CDK6 and MAPK4) and developmental processes (BMP4, HAND1, EOMES, ID2, GATA4, GATA5, ISL1 and MSX1). A comparison of positively regulated OCT4 targets common to EC and ES cells identified genes such as NANOG, PHC1, USP44, SOX2, PHF17 and OCT4, thus further confirming their universal role in maintaining self-renewal in both cell types. Finally we have created a user-friendly database (http://biit.cs.ut.ee/escd/), integrating all OCT4 and stem cell related datasets in both human and mouse ES and EC cells.In the current era of systems biology driven research, we envisage that our integrated embryonic stem cell database will prove beneficial to the booming field of ES, iPS and cancer research.Marc JungHedi PetersonLukas ChavezPascal KahlemHans LehrachJaak ViloJames AdjayePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 5, p e10709 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marc Jung Hedi Peterson Lukas Chavez Pascal Kahlem Hans Lehrach Jaak Vilo James Adjaye A data integration approach to mapping OCT4 gene regulatory networks operative in embryonic stem cells and embryonal carcinoma cells.
description	It is essential to understand the network of transcription factors controlling self-renewal of human embryonic stem cells (ESCs) and human embryonal carcinoma cells (ECs) if we are to exploit these cells in regenerative medicine regimes. Correlating gene expression levels after RNAi-based ablation of OCT4 function with its downstream targets enables a better prediction of motif-specific driven expression modules pertinent for self-renewal and differentiation of embryonic stem cells and induced pluripotent stem cells.We initially identified putative direct downstream targets of OCT4 by employing CHIP-on-chip analysis. A comparison of three peak analysis programs revealed a refined list of OCT4 targets in the human EC cell line NCCIT, this list was then compared to previously published OCT4 CHIP-on-chip datasets derived from both ES and EC cells. We have verified an enriched POU-motif, discovered by a de novo approach, thus enabling us to define six distinct modules of OCT4 binding and regulation of its target genes.A selection of these targets has been validated, like NANOG, which harbours the evolutionarily conserved OCT4-SOX2 binding motif within its proximal promoter. Other validated targets, which do not harbour the classical HMG motif are USP44 and GADD45G, a key regulator of the cell cycle. Over-expression of GADD45G in NCCIT cells resulted in an enrichment and up-regulation of genes associated with the cell cycle (CDKN1B, CDKN1C, CDK6 and MAPK4) and developmental processes (BMP4, HAND1, EOMES, ID2, GATA4, GATA5, ISL1 and MSX1). A comparison of positively regulated OCT4 targets common to EC and ES cells identified genes such as NANOG, PHC1, USP44, SOX2, PHF17 and OCT4, thus further confirming their universal role in maintaining self-renewal in both cell types. Finally we have created a user-friendly database (http://biit.cs.ut.ee/escd/), integrating all OCT4 and stem cell related datasets in both human and mouse ES and EC cells.In the current era of systems biology driven research, we envisage that our integrated embryonic stem cell database will prove beneficial to the booming field of ES, iPS and cancer research.
format	article
author	Marc Jung Hedi Peterson Lukas Chavez Pascal Kahlem Hans Lehrach Jaak Vilo James Adjaye
author_facet	Marc Jung Hedi Peterson Lukas Chavez Pascal Kahlem Hans Lehrach Jaak Vilo James Adjaye
author_sort	Marc Jung
title	A data integration approach to mapping OCT4 gene regulatory networks operative in embryonic stem cells and embryonal carcinoma cells.
title_short	A data integration approach to mapping OCT4 gene regulatory networks operative in embryonic stem cells and embryonal carcinoma cells.
title_full	A data integration approach to mapping OCT4 gene regulatory networks operative in embryonic stem cells and embryonal carcinoma cells.
title_fullStr	A data integration approach to mapping OCT4 gene regulatory networks operative in embryonic stem cells and embryonal carcinoma cells.
title_full_unstemmed	A data integration approach to mapping OCT4 gene regulatory networks operative in embryonic stem cells and embryonal carcinoma cells.
title_sort	data integration approach to mapping oct4 gene regulatory networks operative in embryonic stem cells and embryonal carcinoma cells.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/890cfceae9924bf3bc0cb21af66d9b3d
work_keys_str_mv	AT marcjung adataintegrationapproachtomappingoct4generegulatorynetworksoperativeinembryonicstemcellsandembryonalcarcinomacells AT hedipeterson adataintegrationapproachtomappingoct4generegulatorynetworksoperativeinembryonicstemcellsandembryonalcarcinomacells AT lukaschavez adataintegrationapproachtomappingoct4generegulatorynetworksoperativeinembryonicstemcellsandembryonalcarcinomacells AT pascalkahlem adataintegrationapproachtomappingoct4generegulatorynetworksoperativeinembryonicstemcellsandembryonalcarcinomacells AT hanslehrach adataintegrationapproachtomappingoct4generegulatorynetworksoperativeinembryonicstemcellsandembryonalcarcinomacells AT jaakvilo adataintegrationapproachtomappingoct4generegulatorynetworksoperativeinembryonicstemcellsandembryonalcarcinomacells AT jamesadjaye adataintegrationapproachtomappingoct4generegulatorynetworksoperativeinembryonicstemcellsandembryonalcarcinomacells AT marcjung dataintegrationapproachtomappingoct4generegulatorynetworksoperativeinembryonicstemcellsandembryonalcarcinomacells AT hedipeterson dataintegrationapproachtomappingoct4generegulatorynetworksoperativeinembryonicstemcellsandembryonalcarcinomacells AT lukaschavez dataintegrationapproachtomappingoct4generegulatorynetworksoperativeinembryonicstemcellsandembryonalcarcinomacells AT pascalkahlem dataintegrationapproachtomappingoct4generegulatorynetworksoperativeinembryonicstemcellsandembryonalcarcinomacells AT hanslehrach dataintegrationapproachtomappingoct4generegulatorynetworksoperativeinembryonicstemcellsandembryonalcarcinomacells AT jaakvilo dataintegrationapproachtomappingoct4generegulatorynetworksoperativeinembryonicstemcellsandembryonalcarcinomacells AT jamesadjaye dataintegrationapproachtomappingoct4generegulatorynetworksoperativeinembryonicstemcellsandembryonalcarcinomacells
_version_	1718374118815956992

A data integration approach to mapping OCT4 gene regulatory networks operative in embryonic stem cells and embryonal carcinoma cells.

Ejemplares similares