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Reduced Oct4 expression directs a robust pluripotent state with distinct signaling pathway activity and increased Oct4 and Nanog enhancer occupancy

ABSTRACT: Analysis of Oct4(Pou5f1)-dependent gene expression levels in mouse embryonic stem cells (ESCs). In order to robustly assess changes in gene expression levels orchestrated by the transcription factor Oct4, we used microarrays to profile the transcriptional activity of four ESC lines: Two of these cell lines have been genetically engineered to express Oct4 at reduced levels (Oct+/-: OKO160 and ZHTc6), while the other two were expressing Oct4 at wild-type levels (Oct4+/+: E14Tg2a and OctGIP). Genes that showed significant and consistent changes between the Oct4-states were considered putative transcriptional targets of Oct4.

ORGANISM(S): Mus musculus

SUBMITTER: Florian Halbritter

PROVIDER: E-MTAB-1619 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Reduced Oct4 expression directs a robust pluripotent state with distinct signaling activity and increased enhancer occupancy by Oct4 and Nanog.

Karwacki-Neisius Violetta V Göke Jonathan J Osorno Rodrigo R Halbritter Florian F Ng Jia Hui JH Weiße Andrea Y AY Wong Frederick C K FC Gagliardi Alessia A Mullin Nicholas P NP Festuccia Nicola N Colby Douglas D Tomlinson Simon R SR Ng Huck-Hui HH Chambers Ian I

Cell stem cell 20130501 5

Embryonic stem cell (ESC) pluripotency is governed by a gene regulatory network centered on the transcription factors Oct4 and Nanog. To date, robust self-renewing ESC states have only been obtained through the chemical inhibition of signaling pathways or enforced transgene expression. Here, we show that ESCs with reduced Oct4 expression resulting from heterozygosity also exhibit a stabilized pluripotent state. Despite having reduced Oct4 expression, Oct4(+/-) ESCs show increased genome-wide bin ...[more]

PMID: 23642364

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