title: Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development.
abstract: The Tet family of enzymes (Tet1/2/3) converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Mouse embryonic stem cells (mESCs) highly express Tet1 and have an elevated level of 5hmC. Tet1 has been implicated in ESC maintenance and lineage specification in vitro but its precise function in development is not well defined. To establish the role of Tet1 in pluripotency and development, we have generated Tet1 mutant mESCs and mice. Tet1(-/-) ESCs have reduced levels of 5hmC and subtle changes in global gene expression, and are pluripotent and support development of live-born mice in tetraploid complementation assay, but display skewed differentiation toward trophectoderm in vitro. Tet1 mutant mice are viable, fertile, and grossly normal, though some mutant mice have a slightly smaller body size at birth. Our data suggest that Tet1 loss leading to a partial reduction in 5hmC levels does not affect pluripotency in ESCs and is compatible with embryonic and postnatal development.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Meelad M
authors.initials: MM
authors.lastname: Dawlaty
authors.forename: Kibibi
authors.initials: K
authors.lastname: Ganz
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Powell
authors.forename: Yueh-Chiang
authors.initials: YC
authors.lastname: Hu
authors.forename: Styliani
authors.initials: S
authors.lastname: Markoulaki
authors.forename: Albert W
authors.initials: AW
authors.lastname: Cheng
authors.forename: Qing
authors.initials: Q
authors.lastname: Gao
authors.forename: Jongpil
authors.initials: J
authors.lastname: Kim
authors.forename: Sang-Woon
authors.initials: SW
authors.lastname: Choi
authors.forename: David C
authors.initials: DC
authors.lastname: Page
authors.forename: Rudolf
authors.initials: R
authors.lastname: Jaenisch
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000818:Animals; D000831:Animals, Newborn; D049628:Body Size; D003596:Cytosine / Q000031:analogs & derivatives / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005298:Fertility; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D005816:Genetic Complementation Test; D051379:Mice; D008810:Mice, Inbred C57BL; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000378:metabolism*; D057891:Tetraploidy
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C540839:TET1 protein, mouse; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine