Genomic imprinting and transcription factor YY1

Joomyeong Kim, Louisiana State University


Genomic imprinting is an unusual mechanism by which one allele is repressed on the basis of its parental origin. Imprinted genes are usually clustered in chromosomal regions, and a given domain is co-regulated through small genomic regions termed imprinting control regions (ICRs). ICRs obtain parental imprinting marks during gametogenesis in the form of DNA methylation and histone modifications. We previously discovered that unusual clusters of YY1 binding sites are localized within several ICRs, including Xist, Nespas, and Peg3, and also that these YY1-associated ICRs are all methylated during oogenesis. In the past few years, we have performed a series of in vivo YY1 knockdown experiments to investigate potential YY1 roles in DNA methylation of these ICRs. According to the latest results derived from conditional YY1 knockdown experiments, the reduced levels of YY1 during oogenesis resulted in a target-specific loss of DNA methylation on Peg3 and Xist. In contrast, the YY1 knockdown during spermatogenesis did not cause any major change in the DNA methylation levels of these ICRs. These studies suggest that YY1 likely plays a role in establishing DNA methylation of Peg3 and Xist during oogenesis, and further suggest that the clusters of YY1 binding sites of Peg3 and Xist might serve as a recruiting signal for de novo DNA methylation machineries. © 2010 by Begell House, Inc.