title: TRIM28 Controls Genomic Imprinting through Distinct Mechanisms during and after Early Genome-wide Reprogramming.
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.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Alexander
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Maho
authors.initials: M
authors.lastname: Shibata
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Clark
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA. Electronic address: garciamj@cornell.edu.
authors.forename: María J
authors.initials: MJ
authors.lastname: García-García
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming; D019175:DNA Methylation; D016678:Genome; D018392:Genomic Imprinting; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D000076183:Tripartite Motif-Containing Protein 28
chemical_list: D009687:Nuclear Proteins; D012097:Repressor Proteins; C103190:Trim28 protein, mouse; D000076183:Tripartite Motif-Containing Protein 28