Orphan nuclear receptor LRH-1 is required to maintain Oct4 expression at the epiblast stage of embryonic development.

TitleOrphan nuclear receptor LRH-1 is required to maintain Oct4 expression at the epiblast stage of embryonic development.
Publication TypeJournal Article
Year of Publication2005
AuthorsGu, P, Goodwin, B, Chung, AC-K, Xu, X, Wheeler, DA, Price, RR, Galardi, C, Peng, L, Latour, AM, Koller, BH, Gossen, J, Kliewer, SA, Cooney, AJ
JournalMol Cell Biol
Volume25
Issue9
Pagination3492-505
Date Published2005 May
ISSN0270-7306
KeywordsAnimals, Blastocyst, Cell Differentiation, DNA-Binding Proteins, Down-Regulation, Embryo, Mammalian, Embryonic Development, Gene Expression Regulation, Developmental, Gene Silencing, Genes, Lethal, Mice, Octamer Transcription Factor-3, Receptors, Cytoplasmic and Nuclear, Response Elements, Stem Cells, Transcription Factors, Up-Regulation
Abstract

Oct4 plays an essential role in maintaining the inner cell mass and pluripotence of embryonic stem (ES) cells. The expression of Oct4 is regulated by the proximal enhancer and promoter in the epiblast and by the distal enhancer and promoter at all other stages in the pluripotent cell lineage. Here we report that the orphan nuclear receptor LRH-1, which is expressed in undifferentiated ES cells, can bind to SF-1 response elements in the proximal promoter and proximal enhancer of the Oct4 gene and activate Oct4 reporter gene expression. LRH-1 is colocalized with Oct4 in the inner cell mass and the epiblast of embryos at early developmental stages. Disruption of the LRH-1 gene results in loss of Oct4 expression at the epiblast stage and early embryonic death. Using LRH-1(-/-) ES cells, we also show that LRH-1 is required to maintain Oct4 expression at early differentiation time points. In vitro and in vivo results show that LRH-1 plays an essential role in the maintenance of Oct4 expression in ES cells at the epiblast stage of embryonic development, thereby maintaining pluripotence at this crucial developmental stage prior to segregation of the primordial germ cell lineage at gastrulation.

DOI10.1128/MCB.25.9.3492-3505.2005
Alternate JournalMol. Cell. Biol.
PubMed ID15831456
PubMed Central IDPMC1084298
Grant ListDK 62434 / DK / NIDDK NIH HHS / United States
U19 DK062434 / DK / NIDDK NIH HHS / United States
U54 HD007495 / HD / NICHD NIH HHS / United States
DK 57743 / DK / NIDDK NIH HHS / United States
P01 DK057743 / DK / NIDDK NIH HHS / United States
U54 HD 07495-31 / HD / NICHD NIH HHS / United States