YY1's role in the Peg3 imprinted domain

Area of Science:

• Genetics
• Epigenetics
• Developmental Biology

Background:

• The Imprinting Control Region (ICR) of the Peg3 (Paternally Expressed Gene 3) domain features a unique cluster of YY1 binding sites.
• The precise function of these YY1 binding sites within the Peg3 ICR remains largely uncharacterized.

Purpose of the Study:

• To elucidate the functional significance of the YY1 binding sites within the mouse Peg3 ICR.
• To determine the role of YY1 in regulating imprinting, DNA methylation, and gene expression within the Peg3 domain.

Main Methods:

• Site-directed mutagenesis was employed to alter the YY1 binding sites within the Peg3 ICR.
• Analysis of pup survival, DNA methylation patterns at the ICR, imprinting status, and gene expression levels (Peg3, Usp29, Zim1) following paternal and maternal transmission of the mutant allele.

Main Results:

• Mutating YY1 binding sites did not impact pup survival or the establishment/maintenance of maternal-specific DNA methylation at the ICR.
• Paternal transmission of the mutant allele led to altered expression of Peg3, Usp29, and Zim1, with effects more pronounced neonatally and differing between sexes.
• YY1's primary role was identified in controlling transcriptional levels, rather than DNA methylation, within the Peg3 domain.

Conclusions:

• YY1 is crucial for regulating the transcriptional output of genes within the Peg3 domain.
• YY1's influence on Peg3 domain gene expression is independent of its role in establishing or maintaining ICR DNA methylation.
• Sex-specific differences in gene expression changes suggest differential involvement of YY1 in males and females concerning the Peg3 domain.