Title: Rex1/Zfp42 as an epigenetic regulator for genomic imprinting.

Authors: Kim, Jeong Do; Kim, Hana; Ekram, Muhammad B; Yu, Sungryul; Faulk, Christopher; Kim, Joomyeong

Published In Hum Mol Genet, (2011 Apr 01)

Abstract: Zfp42/Rex1 (reduced expression gene 1) is a well-known stem-cell marker that has been duplicated from YY1 in the eutherian lineage. In the current study, we characterized the in vivo roles of Rex1 using a mutant mouse line disrupting its transcription. In contrast to the ubiquitous expression of YY1, Rex1 is expressed only during spermatogenesis and early embryogenesis and also in a very limited area of the placenta. Yet, the gene dosage of Rex1 is very critical for the survival of the late-stage embryos and neonates. This delayed phenotypic consequence suggests potential roles for Rex1 in establishing and maintaining unknown epigenetic modifications. Consistently, Rex1-null blastocysts display hypermethylation in the differentially methylated regions (DMRs) of Peg3 and Gnas imprinted domains, which are known to contain YY1 binding sites. Further analyses confirmed in vivo binding of Rex1 only to the unmethylated allele of these two regions. Thus, Rex1 may function as a protector for these DMRs against DNA methylation. Overall, the functional connection of Rex1 to genomic imprinting represents another case where newly made genes have co-evolved with lineage-specific phenomena.

PubMed ID: 21233130

MeSH Terms: Alleles*; Animals; Blastocyst/cytology; Blastocyst/metabolism*; Chromogranins; DNA Methylation/physiology*; GTP-Binding Protein alpha Subunits, Gs/genetics; GTP-Binding Protein alpha Subunits, Gs/metabolism; Genomic Imprinting/physiology*; Humans; Kruppel-Like Transcription Factors/metabolism; Mice; Mice, Mutant Strains; Transcription Factors/genetics; Transcription Factors/metabolism*