title: Nr0b1 is a negative regulator of Zscan4c in mouse embryonic stem cells.
abstract: Nuclear receptor subfamily 0, group B, member 1 (Nr0b1, also known as Dax1) is regarded as an important component of the transcription factor network that governs pluripotency in mouse embryonic stem (ES) cells. Here we generated inducible knockout ES cells for Nr0b1 using the Cre-loxP system and analyzed its precise function. We succeeded in establishing the Nr0b1-null ES cells and confirmed their pluripotency by showing their contribution to chimeric embryos. However, they proliferated slowly with over-expression of 2-cell stage specific transcripts including Zscan4c, which is known to be involved in telomere elongation in ES cells. We revealed that over-expression of Zscan4c prevents normal self-renewal by inducing arrest at G2 phase followed by cell death and that Nr0b1 directly represses the Zscan4c promoter. These data indicated that Nr0b1 is not essential to maintain pluripotency but is involved in the proper activation of 2-cell specific transcripts for self-renewal.
authors.affiliation: 1] Laboratory for Pluripotent Stem Cell Studies, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan [2] JST, CREST, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
authors.forename: Setsuko
authors.initials: S
authors.lastname: Fujii
authors.affiliation: 1] Laboratory for Pluripotent Stem Cell Studies, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan [2] JST, CREST, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Nishikawa-Torikai
authors.affiliation: Laboratory for Pluripotent Stem Cell Studies, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Futatsugi
authors.affiliation: 1] Laboratory for Pluripotent Stem Cell Studies, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan [2] Division of Embryology, National Institute for Basic Biology (NIBB), Okazaki 444-8787, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Toyooka
authors.affiliation: Laboratory for Pluripotent Stem Cell Studies, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Yamane
authors.affiliation: Laboratory for Pluripotent Stem Cell Studies, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohtsuka
authors.affiliation: 1] Laboratory for Pluripotent Stem Cell Studies, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan [2] Laboratory for Development and Regenerative Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunokicho, Chuo-ku, Kobe 650-0017, Japan [3] JST, CREST, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Niwa
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D016923:Cell Death / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D000066673:Cell Self Renewal; D057137:DAX-1 Orphan Nuclear Receptor / Q000235:genetics / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D023061:Gene Order; D018390:Gene Targeting; D056426:Genetic Loci; D051379:Mice; D010641:Phenotype; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; C539966:Nr0b1 protein, mouse; D014157:Transcription Factors; C000588925:Zscan4c protein, mouse