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Cell Rep. 2015 Nov 10;13(6):1194-1205. doi: 10.1016/j.celrep.2015.09.078. Epub 2015 Oct 29.

TRIM28 Controls Genomic Imprinting through Distinct Mechanisms during and after Early Genome-wide Reprogramming.

Author information

1
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
2
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA. Electronic address: garciamj@cornell.edu.

Abstract

Genomic imprinting depends on the establishment and maintenance of DNA methylation at imprinting control regions. However, the mechanisms by which these heritable marks influence allele-specific expression are not fully understood. By analyzing maternal, zygotic, maternal-zygotic, and conditional Trim28 mutants, we found that the transcription factor TRIM28 controls genomic imprinting through distinct mechanisms at different developmental stages. During early genome-wide reprogramming, both maternal and zygotic TRIM28 are required for the maintenance of methylation at germline imprints. However, in conditional Trim28 mutants, Gtl2-imprinted gene expression was lost despite normal methylation levels at the germline IG-DMR. These results provide evidence that TRIM28 controls imprinting after early embryonic reprogramming through a mechanism other than the maintenance of germline imprints. Additionally, our finding that secondary imprints were hypomethylated in TRIM28 mutants uncovers a requirement of TRIM28 after genome-wide reprogramming for interpreting germline imprints and regulating DNA methylation at imprinted gene promoters.

PMID:
26527006
PMCID:
PMC4644443
DOI:
10.1016/j.celrep.2015.09.078
[Indexed for MEDLINE]
Free PMC Article

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