Abstract
Peg3 (Paternally Expressed Gene 3) is an imprinted gene that encodes a zinc finger DNA-binding protein. Peg3 itself is localized in the middle of a KRAB-A (Kruppel-Associated Box) zinc finger gene cluster. The amino acid sequence encoded by its exon 7 also shows sequence similarity to that of KRAB-A, suggesting Peg3 as a KRAB-containing zinc finger gene. As predicted, the PEG3 protein was co-immunoprecipitated with KAP1, a co-repressor that interacts with KRAB-A. A series of follow-up experiments further demonstrated that the exon 7 of PEG3 is indeed responsible for its physical interaction with KAP1. ChIP and promoter assays also indicated that PEG3 likely controls its downstream genes through the KAP1-mediated repression mechanism. Overall, the current study identifies PEG3 as a KRAB-containing zinc finger protein that interacts with the co-repressor protein KAP1.
Highlights
Peg3 (Paternally Expressed Gene 3) is an imprinted gene that encodes a zinc finger DNA-binding protein [1, 2]
A series of follow-up experiments further demonstrated that this divergent KRAB-A is functional as a subdomain recruiting KAP1, and suggest that this domain might be critical for the repression function of PEG3
This is consistent with the pattern observed from the other Kruppeltype zinc finger proteins [25, 26], and further suggests that those conserved ZF motifs are likely involved in DNA binding
Summary
Peg (Paternally Expressed Gene 3) is an imprinted gene that encodes a zinc finger DNA-binding protein [1, 2]. The genomic region surrounding the promoter of Peg is usually methylated during oogenesis, the paternal allele is mainly expressed and functional in somatic cells [3,4,5]. Recent studies revealed that this protein functions as a repressor controlling the transcriptional rates of its downstream genes [1, 2]. This has been further supported by the observation that the mutant embryos lacking PEG3 tend to de-repress several placenta-specific gene families in the brain [7]. The detailed mechanisms for the predicted repression are currently unknown
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