Abstract
Usp29 (Ubiquitin-specific protease 29) is a paternally expressed gene located upstream of another imprinted gene Peg3. In the current study, the transcription of this long coding gene spanning a 250-kb genomic distance was truncated using a knockin allele. According to the results, paternal transmission of the mutant allele resulted in reduced body and litter sizes whereas the maternal transmission caused no obvious effects. In the paternal mutant, the expression levels of Usp29 were reduced to 14–18% level of the wild-type littermates due to the Poly-A signal included in the knockin cassette. Expression analyses further revealed an unusual female-specific up-regulation of the adjacent imprinted gene Zfp264 in the mutant. Consistent with this, the promoter of Zfp264 was hypomethylated only in the female mutant. Interestingly, this female-specific hypomethylation by the knockin allele was not detected in the offspring of an interspecific crossing, indicating its sensitivity to genetic background. Overall, the results suggest that the transcription of Usp29 may be involved in DNA methylation setting of Zfp264 promoter in a sex-specific manner.
Highlights
Usp29 (Ubiquitin-Specific Protease 29) is an imprinted gene located in the proximal mouse chromosome 7/human chromosome 19q13.4 [1]
The primer set detecting the 1st exon of Usp29 (RT-1a/b) before the neomycin resistance gene (NeoR) cassette did not show any major difference in the expression levels between the wild-type littermates and the heterozygotes inheriting the knockin allele paternally (Fig 2B)
The results suggest that the transcription of Usp29 might be involved in DNA methylation setting of the promoter of Zfp264 in a sex-specific manner
Summary
Usp (Ubiquitin-Specific Protease 29) is an imprinted gene located in the proximal mouse chromosome 7/human chromosome 19q13.4 [1]. This gene is located upstream of another imprinted gene Peg (Paternally Expressed Gene 3) In mice, both genes share their bi-directional promoter, and the 4-kb genomic region surrounding this promoter is methylated during oogenesis and inherited as a gametic signal [2, 3]. Both genes share their bi-directional promoter, and the 4-kb genomic region surrounding this promoter is methylated during oogenesis and inherited as a gametic signal [2, 3] As a consequence, both genes are expressed mainly from the paternal allele in somatic cells [1]. Consistent with this, recent in vitro studies have identified human USP29 as an enzyme removing ubiquitin and subsequently stabilizing the protein level of Claspin, a key component controlling the DNA damage checkpoint pathway [4]. This is consistent with the observations that human USP29 might modulate the protein levels of p53 [5]
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