title: miR-29 regulates Tet1 expression and contributes to early differentiation of mouse ESCs.
abstract: The ten-eleven translocation-1 (Tet1), which converts 5-methylcytosine (5mC) to 5-hydroxymethycytosine (5hmC), plays important roles in many important biological processes, such as mouse embryonic stem cells (ESCs) maintenance. However, the mechanisms for Tet-1 regulation remain largely unknown. Here we showed that miR-29 family (miR-29a, miR-29b and miR-29c) can directly repress Tet1 expression. We found that Tet1 was highly expressed and 5hmC was presented at relatively high levels in mouse ESCs, but the levels of both Tet1 and 5hmC were reduced during the early differentiation of ESCs. On the contrary, miR-29 level was increased in this process. ESCs stably transfecting with miR-29 precursors showed lower levels of Tet1 protein and 5hmC. Furthermore, we demonstrated that miR-29 overexpression selectively affected cell lineage markers and skewed ESC differentiation, which was similar in Tet1 knockdown ESCs. Our results indicate that miR-29 is a direct regulator of Tet1 in mouse ESCs.
authors.affiliation: Center for Translational Research on Neurological Diseases, the First Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Dehua
authors.initials: D
authors.lastname: Yang
authors.affiliation: Center for Translational Research on Neurological Diseases, the First Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.affiliation: Center for Translational Research on Neurological Diseases, the First Affiliated Hospital, Dalian Medical University, Dalian, China.|Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|Collaborative Innovation Center for Brain Science, the First Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Le
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D000943:Antigens, Differentiation; D004268:DNA-Binding Proteins; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; C540839:TET1 protein, mouse; D044503:5-Methylcytosine
keywords: 5hmC; Tet1; embryonic stem cells; miR-29 family