Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptional regulation of Tet1 during development


ABSTRACT: 5-hydroxymethylcytosine (5hmC) is a recently discovered epigenetic modification that is lost in human cancers. Formation of 5hmC is catalysed by the Ten eleven translocation (TET) proteins that mediate the sequential oxidation of 5-methylcytosine (5mC) to 5hmC, leading to eventual DNA demethylation. Several mechanisms can lead to loss of 5hmC in cancers, including mutations in IDH or TET2 genes. However, little is known about the role of TET proteins and 5hmC in adult cells. Here, we report that TET1 downmodulation is required to permit adult cells to proliferate. TET1 is rapidly downmodulated in proliferating primary cells and in regenerating liver. TET1 silencing accelerates cell cycle progression while its constitutive expression inhibits cell growth. TET1 is a negative regulator of cell proliferation and it is regulated during development in tissue specific manner. These findings enlarge our knowledge on how one epigenetic modification such as the DNA hydroxymethylation mediated by TET1 is a key player on the control of cell proliferation. Examination of 5hmC in MEF at passage 0 and at passage 5.

ORGANISM(S): Mus musculus

SUBMITTER: Francesco Neri 

PROVIDER: E-GEOD-57250 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

TET1 is controlled by pluripotency-associated factors in ESCs and downmodulated by PRC2 in differentiated cells and tissues.

Neri Francesco F   Incarnato Danny D   Krepelova Anna A   Dettori Daniela D   Rapelli Stefania S   Maldotti Mara M   Parlato Caterina C   Anselmi Francesca F   Galvagni Federico F   Oliviero Salvatore S  

Nucleic acids research 20150429 14


Ten-eleven translocation (Tet) genes encode for a family of hydroxymethylase enzymes involved in regulating DNA methylation dynamics. Tet1 is highly expressed in mouse embryonic stem cells (ESCs) where it plays a critical role the pluripotency maintenance. Tet1 is also involved in cell reprogramming events and in cancer progression. Although the functional role of Tet1 has been largely studied, its regulation is poorly understood. Here we show that Tet1 gene is regulated, both in mouse and human  ...[more]

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