title: Dynamics of ten-eleven translocation hydroxylase family proteins and 5-hydroxymethylcytosine in oligodendrocyte differentiation.
abstract: The ten-eleven translocation (TET) family of methylcytosine dioxygenases catalyze oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and promote DNA demethylation. Despite the abundance of 5hmC and TET proteins in the brain, little is known about their role in oligodendrocytes (OLs). Here, we analyzed TET expression during OL development in vivo and in vitro, and found that three TET family members possess unique subcellular and temporal expression patterns. Furthermore, the level of 5hmC exhibits dynamic changes during OL maturation, which implies that 5hmC modification may play a role in the expression of critical genes necessary for OL maturation. siRNA-mediated silencing of the TET family proteins in OLs demonstrated that each of the TET proteins is required for OL differentiation. However, based on their unique domain structures, we speculate that the three TET members may function by different mechanisms. In summary, we have established the temporal expression of TET proteins and the dynamic level of 5hmC during OL development and demonstrate that all three TET members are necessary for OL differentiation.
authors.affiliation: Institute of Neuroscience, Fourth Military Medical University, Xi'an, China.
authors.forename: Xianghui
authors.initials: X
authors.lastname: Zhao
authors.forename: Jinxiang
authors.initials: J
authors.lastname: Dai
authors.forename: Yue
authors.initials: Y
authors.lastname: Ma
authors.forename: Yajing
authors.initials: Y
authors.lastname: Mi
authors.forename: Daxiang
authors.initials: D
authors.lastname: Cui
authors.forename: Gong
authors.initials: G
authors.lastname: Ju
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Macklin
authors.forename: Weilin
authors.initials: W
authors.lastname: Jin
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D049308:Dioxygenases / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D051379:Mice; D006899:Mixed Function Oxygenases; D008969:Molecular Sequence Data; D009836:Oligodendroglia / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D006899:Mixed Function Oxygenases; C462539:TET1 protein, human; C578792:TET3 protein, human; D049308:Dioxygenases; C541081:TET2 protein, human
keywords: 5hmC; DNA hydroxylase; epigenetic regulation; oligodendrocyte development