title: Roles for Tbx3 in regulation of two-cell state and telomere elongation in mouse ES cells.
abstract: Mouse embryonic stem (ES) cell cultures exhibit heterogeneity and recently are discovered to sporadically enter the 2-cell (2C)-embryo state, critical for ES potency. Zscan4 could mark the sporadic 2C-state of ES cells. However, factors that regulate the Zscan4(+)/2C state remain to be elucidated. We show that Tbx3 plays a novel role in regulation of Zscan4(+)/2C state. Tbx3 activates 2-cell genes including Zscan4 and Tcstv1/3, but not vise versa. Ectopic expression of Tbx3 results in telomere elongation, consistent with a role for Zscan4 in telomere lengthening. Mechanistically, Tbx3 decreases Dnmt3b and increases Tet2 protein levels, and reduces binding of Dnmt3b to subtelomeres, resulting in reduced DNA methylation and derepression of genes at subtelomeres, e.g. Zscan4. These data suggest that Tbx3 can activate Zscan4(+)/2C state by negative regulation of DNA methylation at repeated sequences, linking to telomere maintenance and self-renewal of ES cells.
authors: State Key Laboratory of Medicinal Chemical Biology; Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors: Jiameng
authors: J
authors: Dan
authors: State Key Laboratory of Medicinal Chemical Biology; Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors: Minshu
authors: M
authors: Li
authors: State Key Laboratory of Medicinal Chemical Biology; Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors: Jiao
authors: J
authors: Yang
authors: State Key Laboratory of Medicinal Chemical Biology; Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors: Jiaojiao
authors: J
authors: Li
authors: Department of Obstetrics and Gynecology, University of South Florida College of Medicine, Tampa, FL 33612, USA.
authors: Maja
authors: M
authors: Okuka
authors: State Key Laboratory of Medicinal Chemical Biology; Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors: Xiaoying
authors: X
authors: Ye
authors: State Key Laboratory of Medicinal Chemical Biology; Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors: Lin
authors: L
authors: Liu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D051379:Mice; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D059505:Telomere Homeostasis; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation
chemical_list: D020825:T-Box Domain Proteins; C491460:Tbx3 protein, mouse; D014157:Transcription Factors; C000588925:Zscan4c protein, mouse; D019098:Telomerase