Genomic imprinting of p57KIP2, a cyclin–dependent kinase inhibitor, in mouse

Hatada, Izuho; Mukai, Tsunehiro

doi:10.1038/ng1095-204

Cited by 272 publications

(160 citation statements)

References 24 publications

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“…3b,d). These data extend previous observations from methyl-sensitive restriction digests that showed parent-of-origin methylation at three sites in the Cdkn1c coding sequence 17 . In Eed -/-embryos, parent-of-origin methylation was present, but there were specific changes in the methylation pattern when compared with that of their wild-type counterparts (Fig.…”

Section: These Data Identify Eed As a Member Of A New Class Of Trans-supporting

confidence: 90%

Genome imprinting regulated by the mouse Polycomb group protein Eed

et al. 2003

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Epigenetic regulation is essential for temporal, tissue-specific and parent-of-origin-dependent gene expression. It has recently been found that the mouse Polycomb group (PcG) gene Eed (embryonic ectoderm development) acts to maintain repression of the imprinted X chromosome. Here, we investigated whether Eed is also required for regulation of autosomal imprinted loci. Expression analyses showed that transcripts from the silent alleles of a subset of paternally repressed genes were present in Eed -/-embryos. Parent-of-origin methylation was preserved in these embryos, but we observed changes in the methylation status of specific CpGs in differentially methylated regions (DMRs) at affected but not at unaffected loci. These data identify Eed as a member of a new class of trans-acting factors that regulate parent-of-origin expression at imprinted loci.A subset of the mouse and human genomes is expressed from only one allele in a parent-oforigin-specific manner. This subset includes imprinted X-chromosome inactivation and autosomal imprinted loci. It has been proposed that this epigenetic regulation is accomplished through covalent modifications of both the DNA and the N-terminal tails of core histones in nucleosomes 1,2 . There are more than 60 identified autosomal imprinted genes, about half of which are paternally repressed and half maternally repressed. Most imprinted genes that have been examined contain at least one DMR located in the 5′ promoter region or in the body of the gene itself 3 . Recently, several proteins (DNA methyltransferases, CpG methyl binding proteins, chromatin insulators) have been identified as trans-acting factors involved in the epigenetic regulation of these loci 4 . Many of these factors either possess or associate with proteins that possess DNA methyltransferase activity. Additionally, recent studies have shown correlations between covalent histone modifications and the transcriptional status of imprinted alleles 5 . In particular, methylation of histone H3 has been associated with the inactive X chromosome 6 .PcG protein complexes are thought to maintain long-term gene silencing during development through alterations of local chromatin structure 7 . In both Drosophila and mammals, recent reports have shown that the Eed/Ezh2 PcG complex contains histone methyltransferase (HMT) activity, methylating histone H3, and that mutations in the SET domain of the Ezh2 fly homolog, E(Z), abolish the enzymatic activity of the complex in vitro [8][9][10] . The Eed/Ezh2 complex has also been shown to interact with histone deacetylases (HDACs; ref. 11). These

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Section: These Data Identify Eed As a Member Of A New Class Of Trans-supporting

confidence: 90%

Genome imprinting regulated by the mouse Polycomb group protein Eed

et al. 2003

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“…Another approach, a screening of the genome by means of the subtraction hybridization method made it possible to isolate two novel mouse paternally expressed genes: Pegl (paternally expressed gene 1), which was mapped to chromosome 6 (Kaneko-Ishino et aL, 1995), and the other, Peg3, mapped to the proximal region of chromosome 7 (Kuroiwa et aL, 1996). Until now, 4 mouse maternally expressing genes, lgf2r, H19, Mash2 and p57 ~w2 (Hatada and Mukai, 1995), and 10 paternally expressing genes, Mas,Igf2,Ins2,Snrpn,Zuf127,Peg3,Pegl,lnsl,CDC25Mm and SP2 have been identified (Table 1).…”

Section: Identification Of Imprinted Genesmentioning

confidence: 99%

Genomic imprinting and its relevance to genetic diseases

Niikawa

1996

Jap J Human Genet

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SummaryGenomic imprinting is a biological phenomenon determined by an evolutionally acquired, underlying system that may control harmonious development and growth in mammals. It is also relevant to some genetic disorders in man. In this article, lines of biological evidence of imprinting, characteristics of the mouse and human imprinted genes, and findings and mechanisms on the occurrence of several human imprinting disorders are reviewed.

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“…Other genes in the region include the paternally expressed insulin-like growth factor 2 (Igf2) and insulin 2 (Ins2) genes and the maternally expressed p57 KIP2 , Kvlqt1, and Mash2 genes (DeChiara et al 1991;Giddings et al 1994;Guillemot et al 1995;Hatada and Mukai 1995;Gould and Pfeifer 1998). A conserved cluster of imprinted genes is found on human chromosome 11p15.5 in the Beckwith-Wiedemann syndrome critical region (Reid et al 1997).…”

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confidence: 99%

Deletion of the H19 differentially methylated domain results in loss of imprinted expression of H19 and Igf2

Thorvaldsen

Duran²,

Bartolomei³

1998

Genes Dev.

613

537

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Differentially methylated sequences associated with imprinted genes are proposed to control genomic imprinting. A 2-kb region located 5 to the imprinted mouse H19 gene is hypermethylated on the inactive paternal allele throughout development. To determine whether this differentially methylated domain (DMD) is required for imprinted expression at the endogenous locus, we have generated mice harboring a 1.6-kb targeted deletion of the DMD and assayed for allelic expression of H19 and the linked, oppositely imprinted Igf2 gene. H19 is activated and Igf2 expression is reduced when the DMD deletion is paternally inherited; conversely, upon maternal transmission of the mutation, H19 expression is reduced and Igf2 is activated. Consistent with the DMD's hypothesized role of setting up the methylation imprint, the mutation also perturbs allele-specific methylation of the remaining H19 sequences. In conclusion, these experiments show that the H19 hypermethylated 5 flanking sequences are required to silence paternally derived H19.Additionally, these experiments demonstrate a novel role for the DMD on the maternal chromosome where it is required for the maximal expression of H19 and the silencing of Igf2. Thus, the H19 differentially methylated sequences are required for both H19 and Igf2 imprinting.

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Genomic imprinting of p57KIP2, a cyclin–dependent kinase inhibitor, in mouse

Cited by 272 publications

References 24 publications

Genome imprinting regulated by the mouse Polycomb group protein Eed

Genome imprinting regulated by the mouse Polycomb group protein Eed

Genomic imprinting and its relevance to genetic diseases

Deletion of the H19 differentially methylated domain results in loss of imprinted expression of H19 and Igf2

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