| First Author | SanMiguel JM | Year | 2018 |
| Journal | Development | Volume | 145 |
| Issue | 7 | PubMed ID | 29530881 |
| Mgi Jnum | J:264121 | Mgi Id | MGI:6191997 |
| Doi | 10.1242/dev.160622 | Citation | SanMiguel JM, et al. (2018) Imprinted gene dysregulation in a Tet1 null mouse model is stochastic and variable in the germline and offspring. Development 145(7):dev160622 |
| abstractText | Imprinted genes are expressed from one parental allele and regulated by differential DNA methylation at imprinting control regions (ICRs). ICRs are reprogrammed in the germline through erasure and re-establishment of DNA methylation. Although much is known about DNA methylation establishment, DNA demethylation is less well understood. Recently, the Ten-Eleven Translocation proteins (TET1-3) have been shown to initiate DNA demethylation, with Tet1(-/-) mice exhibiting aberrant levels of imprinted gene expression and ICR methylation. Nevertheless, the role of TET1 in demethylating ICRs in the female germline and in controlling allele-specific expression remains unknown. Here, we examined ICR-specific DNA methylation in Tet1(-/-) germ cells and ascertained whether abnormal ICR methylation impacted imprinted gene expression in F1 hybrid somatic tissues derived from Tet1(-/-) eggs or sperm. We show that Tet1 deficiency is associated with hypermethylation of a subset of ICRs in germ cells. Moreover, ICRs with defective germline reprogramming exhibit aberrant DNA methylation and biallelic expression of linked imprinted genes in somatic tissues. Thus, we define a discrete set of genomic regions that require TET1 for germline reprogramming and discuss mechanisms for stochastic imprinting defects. |
