University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations Spring 2011 Roles of Protein Factors in Regulation of Imprinted Gene Expression Shu Lin University of Pennsylvaina,
[email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Biology Commons Recommended Citation Lin, Shu, "Roles of Protein Factors in Regulation of Imprinted Gene Expression" (2011). Publicly Accessible Penn Dissertations. 1546. https://repository.upenn.edu/edissertations/1546 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/1546 For more information, please contact
[email protected]. Roles of Protein Factors in Regulation of Imprinted Gene Expression Abstract Genomic imprinting is an important epigenetic phenomenon in which only one parental allele is expressed. Allele-specific DNA methylation often exists in imprinted control regions (ICRs) and is required for properly imprinted expression. Imprinting control in mammals involves an insulator mechanism that requires CTCF or a long ncRNA silencing mechanism. In this dissertation, I studied functions of protein factors in genomic imprinting. First, methylated DNA binding proteins are involved in maintenance of DNA methylation at imprinted loci and required for selective silencing of one specific allele. eW showed that MBD3 was localized to paternal H19 ICR. By RNA interference experiments in preimplantation embryos, we showed that MBD3 and its NuRD complex cofactor MTA2 were required for maintenance of the paternal methylation at the H19 ICR, and for silencing of the paternal H19. MTA2 is also required for Peg3 allelic expression. These results demonstrate new roles of the NuRD complex in genomic imprinting. Moreover, I showed allele-specific associations of MBD1 and Kaiso with imprinted loci, implicating functional requirements of these proteins in imprinted regulation.