Reprogramming with TET

Stower, Hannah

doi:10.1038/nrg3659

Research Highlight
Published: 17 December 2013

Epigenetics

Reprogramming with TET

Hannah Stower

Nature Reviews Genetics volume 15, page 66 (2014)Cite this article

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TET1 is expressed in PGCs and is a member of the ten-eleven translocation (TET) family of proteins that oxidize 5-methylcytosine. The authors investigated a potential role for TET1 in reprogramming PGCs by generating mice from fathers in which Tet1 had been knocked out. They hypothesized that the germline of the fathers would have aberrant imprinting erasure and the offspring of these mice would thus be developmentally affected. Indeed, phenotypic effects on the next generation included early embryonic lethality, placental and growth defects, and postnatal growth retardation.

The authors noted a similarity between the phenotypic effects of the paternal Tet1 knockout and those of the knockout of paternally expressed 10 (Peg10), which is an imprinted gene, and therefore hypothesized that the paternal knockout resulted in a loss of imprinting at Peg10. An RNA sequencing analysis revealed deregulated expression of Peg10, as well as 11–46 of 80 imprinted genes that normally show expression from the paternal allele. In each case, the maternally expressed genes were upregulated and the paternally expressed genes were downregulated, which indicated a 'maternalization' of imprinted genes. The hypothesis that this was because the imprinted genes had increased methylation at the paternal allele was confirmed by bisulphite sequencing. Furthermore, a specific analysis of the placenta indicated that this maternalization was probably responsible for the placental defects, as imprinting deregulation occurred in the relevant genes.

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