TY - JOUR T1 - Maintenance of Paternal Methylation and Repression of the Imprinted H19 Gene Requires MBD3 A1 - Reese, Kimberly J A1 - Lin, Shu A1 - Verona, Raluca I A1 - Schultz, Richard M A1 - Bartolomei, Marisa S Y1 - 2007/08/17 N2 - Author SummaryGenomic imprinting is a specialized system of gene regulation whereby only one copy of a gene is used, either the maternal or the paternal copy. Misregulation of imprinting in humans results in developmental disorders such as Beckwith-Wiedemann Syndrome, and is implicated in many cancers. Study of imprinted genes in mice can lead to a greater understanding of these diseases as well as insight into gene regulation. Many imprinted genes are associated with methylation on the silenced allele. The imprinted gene H19 is maternally expressed and paternally methylated in a region upstream of the promoter known as the differentially methylated domain. This region is required for proper imprinted expression of H19 and its upstream imprinted neighbor Igf2. Our studies have explored the requirement for methyl-CpG binding protein 3 (MBD3) in silencing of the paternal allele. MBD3 is known to be part of a repressive complex that resides at silenced genes. In our experiments, we have shown that MBD3 is required for imprinting of H19, and is also required for the maintenance of methylation on the paternal allele. Finally, the MBD3 protein can be found at the differentially methylated domain. The identification of a protein required for silencing of the paternal allele of H19 is an important step in understanding regulation of this gene. JF - PLOS Genetics JA - PLOS Genetics VL - 3 IS - 8 UR - https://doi.org/10.1371/journal.pgen.0030137 SP - e137 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pgen.0030137 ER -