title: Tet3 CXXC domain and dioxygenase activity cooperatively regulate key genes for Xenopus eye and neural development.
abstract: Ten-Eleven Translocation (Tet) family of dioxygenases dynamically regulates DNA methylation and has been implicated in cell lineage differentiation and oncogenesis. Yet their functions and mechanisms of action in gene regulation and embryonic development are largely unknown. Here, we report that Xenopus Tet3 plays an essential role in early eye and neural development by directly regulating a set of key developmental genes. Tet3 is an active 5mC hydroxylase regulating the 5mC/5hmC status at target gene promoters. Biochemical and structural studies further demonstrate that the Tet3 CXXC domain is critical for specific Tet3 targeting. Finally, we show that the enzymatic activity and CXXC domain are both crucial for Tet3's biological function. Together, these findings define Tet3 as a transcription regulator and reveal a molecular mechanism by which the 5mC hydroxylase and DNA binding activities of Tet3 cooperate to control target gene expression and embryonic development.
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Departments of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Xu
authors.forename: Chao
authors.initials: C
authors.lastname: Xu
authors.forename: Akiko
authors.initials: A
authors.lastname: Kato
authors.forename: Wolfram
authors.initials: W
authors.lastname: Tempel
authors.forename: Jose Garcia
authors.initials: JG
authors.lastname: Abreu
authors.forename: Chuanbing
authors.initials: C
authors.lastname: Bian
authors.forename: Yeguang
authors.initials: Y
authors.lastname: Hu
authors.forename: Di
authors.initials: D
authors.lastname: Hu
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.forename: Tanja
authors.initials: T
authors.lastname: Cerovina
authors.forename: Jianbo
authors.initials: J
authors.lastname: Diao
authors.forename: Feizhen
authors.initials: F
authors.lastname: Wu
authors.forename: Housheng Hansen
authors.initials: HH
authors.lastname: He
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Cui
authors.forename: Erin
authors.initials: E
authors.lastname: Clark
authors.forename: Chun
authors.initials: C
authors.lastname: Ma
authors.forename: Andrew
authors.initials: A
authors.lastname: Barbara
authors.forename: Gert Jan C
authors.initials: GJ
authors.lastname: Veenstra
authors.forename: Guoliang
authors.initials: G
authors.lastname: Xu
authors.forename: Ursula B
authors.initials: UB
authors.lastname: Kaiser
authors.forename: X Shirley
authors.initials: XS
authors.lastname: Liu
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Sugrue
authors.forename: Xi
authors.initials: X
authors.lastname: He
authors.forename: Jinrong
authors.initials: J
authors.lastname: Min
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kato
authors.forename: Yujiang Geno
authors.initials: YG
authors.lastname: Shi
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D049308:Dioxygenases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005123:Eye / Q000196:embryology*; D008969:Molecular Sequence Data; D055495:Neurogenesis; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D029867:Xenopus Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029867:Xenopus Proteins; D049308:Dioxygenases; C578001:TET3 protein, Xenopus