Abstract
BackgroundThe proximal region of murine Chr 2 has long been known to harbour one or more imprinted genes from classic genetic studies involving reciprocal translocations. No imprinted gene had been identified from this region until our study demonstrated that the PcG gene Sfmbt2 is expressed from the paternally inherited allele in early embryos and extraembryonic tissues. Imprinted genes generally reside in clusters near elements termed Imprinting Control Regions (ICRs), suggesting that Sfmbt2 might represent an anchor for a new imprinted domain.ResultsWe analyzed allelic expression of approximately 20 genes within a 3.9 Mb domain and found that Sfmbt2 and an overlapping non-coding antisense transcript are the only imprinted genes in this region. These transcripts represent a very narrow imprinted gene locus. We also demonstrate that rat Sfmbt2 is imprinted in extraembryonic tissues. An interesting feature of both mouse and rat Sfmbt2 genes is the presence of a large block of miRNAs in intron 10. Other mammals, including the bovine, lack this block of miRNAs. Consistent with this association, we show that human and bovine Sfmbt2 are biallelic. Other evidence indicates that pig Sfmbt2 is also not imprinted. Further strengthening the argument for recent evolution of Sfmbt2 is our demonstration that a more distant muroid rodent, Peromyscus also lacks imprinting and the block of miRNAs.ConclusionsThese observations are consistent with the hypothesis that the block of miRNAs are driving imprinting at this locus. Our results are discussed in the context of ncRNAs at other imprinted loci.Accession numbers for Peromyscus cDNA and intron 10 genomic DNA are [Genbank:HQ416417 and Genbank:HQ416418], respectively.
Highlights
The proximal region of murine Chr 2 has long been known to harbour one or more imprinted genes from classic genetic studies involving reciprocal translocations
Imprinted genes generally reside in clusters around a cis acting element called an Imprinting Control Region (ICR) that exerts its effects over a large chromosomal domain
Our results indicate that Sfmbt2 is the only gene within a 4 Mb region that is imprinted, and that we find no evidence of a classical ICR displaying robust germline specific DNA methylation that is preserved after fertilization
Summary
The proximal region of murine Chr 2 has long been known to harbour one or more imprinted genes from classic genetic studies involving reciprocal translocations. Imprinted genes generally reside in clusters near elements termed Imprinting Control Regions (ICRs), suggesting that Sfmbt might represent an anchor for a new imprinted domain. The imprint is reset at each generation when the two haploid genomes are separate, either during gametogenesis or Imprinted genes generally reside in clusters around a cis acting element called an Imprinting Control Region (ICR) that exerts its effects over a large chromosomal domain (up to 4 Mb) (reviewed in [1]). The most common type of tissue specific limitation is to the extraembryonic lineages, exemplified by the placenta and the yolk sac. This latter observation has provided strong support for the idea that the evolutionary origins of imprinting are rooted in extraembryonic tissue biology
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