Asynchronous DNA replication between 15q11.2q12 homologs: cytogenetic evidence for maternal imprinting and delayed replication

Lin, Min-Sheng; Zhang, A.; Fujimoto, Atsuko

doi:10.1007/bf00197413

Cited by 11 publications

(13 citation statements)

References 36 publications

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“…For three clusters (Igf2r, Kcnq1, Dlk1), experimental deletion of the methylated gametic DMR produced no effect. In contrast, deletion of the unmethylated gametic DMR eliminated parental-specific expression causing a loss of lncRNA expression in cis and biallelic mRNA expression (Lin et al 1995;Zwart et al 2001;Fitzpatrick et al 2002). Two clusters (Gnas and Pws) appear to contain more than one gametic DMR and show a more complex behavior, yet they still share some similarities with the pattern presented in Figure 6 (Williamson et al 2006).…”

Section: Genomic Imprinting In Mammalsmentioning

confidence: 68%

Genomic Imprinting in Mammals

Barlow

Bartolomei

2014

Cold Spring Harbor Perspectives in Biology

606

551

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SUMMARYGenomic imprinting affects a subset of genes in mammals and results in a monoallelic, parental-specific expression pattern. Most of these genes are located in clusters that are regulated through the use of insulators or long noncoding RNAs (lncRNAs). To distinguish the parental alleles, imprinted genes are epigenetically marked in gametes at imprinting control elements through the use of DNA methylation at the very least. Imprinted gene expression is subsequently conferred through lncRNAs, histone modifications, insulators, and higher-order chromatin structure. Such imprints are maintained after fertilization through these mechanisms despite extensive reprogramming of the mammalian genome. Genomic imprinting is an excellent model for understanding mammalian epigenetic regulation.

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Section: Genomic Imprinting In Mammalsmentioning

confidence: 68%

Genomic Imprinting in Mammals

Barlow

Bartolomei

2014

Cold Spring Harbor Perspectives in Biology

606

551

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“…Hypermethylated DNA may participate in nuclear-structure-mediated establishment of origins by altering chromatin structure, either through direct DNA conformational effects of methylation (52,79) or through specific protein-DNA interactions. Consistent with methylation-induced changes in chromatin structure are the correlations of DNA methylation with the timing of DNA replication (17,45,48,62), the transcriptional activity of genes (24), and the ability of DNA to undergo homologous recombination (36). Experiments are in progress to test some of these hypotheses.…”

Section: Figmentioning

confidence: 91%

Active Mammalian Replication Origins Are Associated with a High-Density Cluster of ^mCpG Dinucleotides

Rein

Zorbas

DePamphilis

1997

Molecular and Cellular Biology

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ori-␤ is a well-characterized origin of bidirectional replication (OBR) located ϳ17 kb downstream of the dihydrofolate reductase gene in hamster cell chromosomes. The ϳ2-kb region of ori-␤ that exhibits greatest replication initiation activity also contains 12 potential methylation sites in the form of CpG dinucleotides. To ascertain whether DNA methylation might play a role at mammalian replication origins, the methylation status of these sites was examined with bisulfite to chemically distinguish cytosine (C) from 5-methylcytosine ( m C). All of the CpGs were methylated, and nine of them were located within 356 bp flanking the minimal OBR, creating a high-density cluster of m CpGs that was ϳ10 times greater than average for human DNA. However, the previously reported densely methylated island in which all cytosines were methylated regardless of their dinucleotide composition was not detected and appeared to be an experimental artifact. A second OBR, located at the 5 end of the RPS14 gene, exhibited a strikingly similar methylation pattern, and the organization of CpG dinucleotides at other mammalian origins revealed the potential for high-density CpG methylation. Moreover, analysis of bromodeoxyuridine-labeled nascent DNA confirmed that active replication origins were methylated. These results suggest that a high-density cluster of m CpG dinucleotides may play a role in either the establishment or the regulation of mammalian replication origins.At least 16 initiation sites for DNA replication have now been mapped in the chromosomes of mammals (21,32,70). These studies have shown that DNA synthesis is not initiated randomly throughout cellular chromosomes but at specific DNA sites. However, these sites appear more complex than those found in the simpler genomes of bacteria, bacteriophages, yeasts, animal viruses, and mitochondria. Most DNA synthesis is initiated at specific genomic loci that are contained within 0.5 to 2 kb of DNA. These loci represent the functional origins of bidirectional replication (OBR). Replication bubbles also are detected throughout a larger initiation zone, ranging in size from 6 kb to greater than 55 kb, that encompasses the OBR and contains alternative initiation sites. Thus, metazoan cells appear to designate specific chromosomal loci as regions where initiation can occur and then to select from the many potential initiation sites within this region one site (or a small cluster of sites) that acts as a primary origin of DNA replication. What are the parameters that determine where DNA replication begins?Metazoan replication origins are determined at least in part by specific DNA sequences. The same origins that are utilized in cells containing single copies of a unique genetic locus are also utilized in cells containing hundreds of copies of the same locus (12,18,39,72). Moreover, origins can be translocated to other chromosomal sites and still retain their activity (33, 56) and origin activity can be eliminated by deletion of specific sequences (2, 41). Several reports of autonomo...

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“…DNA methylation at CpG dinucleotides in mammalian cells has been implicated as an important component of such pivotal processes as transcription (1), imprinting (2), recombination (3), carcinogenesis (4), development (5), and replication timing (6). CpG methylation is carried out by a methyltransferase that is associated with replication foci in the nucleus (7).…”

mentioning

confidence: 99%

Absence of an Unusual “Densely Methylated Island” at the Hamster dhfr ori-β

Rein

Natale

Gärtner

et al. 1997

Journal of Biological Chemistry

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An unusual "densely methylated island" (DMI), in which all cytosine residues are methylated on both strands for 127-516 base pairs, has been reported at mammalian origins of DNA replication. This report had far-reaching implications in understanding of DNA methylation and DNA replication. For example, since this DMI appeared in about 90% of proliferating cells, but not in stationary cells, it may regulate origin activation. In an effort to confirm and extend these observations, the DMI at the well characterized ori-␤ locus 17 kilobases downstream of the dhfr gene in chromosomes of Chinese hamster ovary cells was checked for methylated cytosines in genomic DNA. The methylation status of this region was examined in randomly proliferating and stationary cells and in cell populations enriched in the G 1 , S, or G 2 ؉ M phases of their cell division cycle. DNA was subjected to 1) cleavage by methylation-sensitive restriction endonucleases, 2) hydrazine modification of cytosines followed by piperidine cleavage, and 3) permanganate modification of 5-methylcytosines ( m C) followed by piperidine cleavage. The permanganate reaction is a novel method for direct detection of m C residues that complements the more commonly used hydrazine method. These methods were capable of detecting m C in 2% of the cells. At the region of the proposed DMI, only one mC at a CpG site was detected. However, the ori-␤ DMI was not detected in any of these cell populations using any of these methods.DNA methylation at CpG dinucleotides in mammalian cells has been implicated as an important component of such pivotal processes as transcription (1), imprinting (2), recombination (3), carcinogenesis (4), development (5), and replication timing (6). CpG methylation is carried out by a methyltransferase that is associated with replication foci in the nucleus (7). In general, this enzyme methylates specifically hemimethylated CpG dinucleotides, although de novo methylation of unmethylated CpG dinucleotides can occur but at a low rate (8). In addition, this enzyme occasionally methylates cytosines in sequences other than CpG (9, 10). However, given the specificity of the mammalian methyltransferase, this non-target methylation should be of little significance in vivo because the pattern of non-CpG methylation will not be maintained during the subsequent round of DNA replication.Recently, an unusual form of DNA methylation has been implicated as an important component of mammalian origins of DNA replication. A densely methylated island (DMI) 1 has been reported at three different mammalian origins of DNA replication (11, 12). These DMIs were found only in proliferating cell populations and consisted of a 127-, 258-, or 516-bp stretch of DNA in which all cytosines were methylated, regardless of their sequence context (12). The discovery of DMIs has several important implications. First, this unprecedented methylation pattern suggested that a second (or modified) methylation enzyme exists in mammalian cells. Interestingly, limited proteolysis of the mamm...

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Asynchronous DNA replication between 15q11.2q12 homologs: cytogenetic evidence for maternal imprinting and delayed replication

Cited by 11 publications

References 36 publications

Genomic Imprinting in Mammals

Genomic Imprinting in Mammals

Active Mammalian Replication Origins Are Associated with a High-Density Cluster of ^mCpG Dinucleotides

Absence of an Unusual “Densely Methylated Island” at the Hamster dhfr ori-β

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Asynchronous DNA replication between 15q11.2q12 homologs: cytogenetic evidence for maternal imprinting and delayed replication

Cited by 11 publications

References 36 publications

Genomic Imprinting in Mammals

Genomic Imprinting in Mammals

Active Mammalian Replication Origins Are Associated with a High-Density Cluster of mCpG Dinucleotides

Absence of an Unusual “Densely Methylated Island” at the Hamster dhfr ori-β

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Active Mammalian Replication Origins Are Associated with a High-Density Cluster of ^mCpG Dinucleotides