Spreading of methylation along DNA

Lindsay, Heather; Adams, Roger

doi:10.1042/bj3200473

Cited by 27 publications

(21 citation statements)

References 19 publications

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“…We confirmed that expression status of selected bar and non-selected cecropin B was independent within the same genomic locations. This means the inactivation of cecropin B does not spread over to the adjacent bar gene, which is consistent with the conclusion of some previous reports (Vain et al, 2002;Kohli et al, 2003) but argues against others (Lindsay et al, 1996).…”

Section: Stability Of Transgene Expression In Crossing Transmissionsupporting

confidence: 81%

Integration and Expression Stability of Transgenes in Hybriding Transmission of Transgenic Rice Plants Produced by Particle Bombardment

Zhao¹,

Guo²,

Wang³

et al. 2011

mpb

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Four transgenic rice lines TR 5, TR 6, Ming B and Jingyin 119 obtained via particle bombardment were used as transgene donors to create hybrids. The integration and expression stability of exotic bar and cecropin B gene in conventional hybriding transmission were investigated by Southern and Northern blotting analyses. The selection marker bar gene was transferred to all hybrids under selection of Basta herbicide. Loss or gain of small hybridization bands (no more than 2.0 kb) of bar gene occurred in some hybrids, but the difference in integration sites of bar gene copies did not influence their stable expression. The non-selection gene cecropin B was stably transferred from the four transgene donors to their resulting hybrids, but expression level was very different. Silencing of cecropin B gene occurred in some hybrids from TR 5, TR 6 and Ming B. In the transgene donor Jingyin 119 and all its resulting hybrids, cecropin B and bar gene were stably expressed. We concluded that the stability of transgene during crossbreeding transmission is mainly determined by the primary transgenic donors and may be affected by recombination.

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Section: Stability Of Transgene Expression In Crossing Transmissionsupporting

confidence: 81%

Integration and Expression Stability of Transgenes in Hybriding Transmission of Transgenic Rice Plants Produced by Particle Bombardment

Zhao¹,

Guo²,

Wang³

et al. 2011

mpb

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“…34,35 The spreading of methylation from the foci of methylated CpG sites has been demonstrated in vitro in cultured cells and in transgenic mice. 24,32,[36][37][38] Methylation spreading has also been observed to occur as a function of aging and neoplasia. 39,40 In the colon, methylation of the MYOD1 CpG island increases progressively with age.…”

Section: Discussionmentioning

confidence: 99%

De novo methylation of an embryonic globin gene during normal development is strand specific and spreads from the proximal transcribed region

Singal

vanWert

2001

Blood

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The recently discovered de novo methyltransferases DNMT3a and DNMT3b have been shown to be critical to embryonic development. However, at a single gene level, little is known about how the methylation pattern is established during development. The avian embryonic -globin gene promoter is completely unmethylated in 4-day-old chicken embryonic erythroid cells, where it is expressed at a high level, and completely methylated in adult erythroid cells, where it is silent. The methylation pattern of the -globin gene promoter, proximal transcribed region, and distal transcribed region on both DNA strands was examined during development in chicken erythroid cells. It was found that de novo methylation targets the CpG-dense proximal transcribed region on the coding (top) strand initially, followed by spreading into the 3 region and into the promoter region. Methylation of the template (bottom) strand lags behind that of the coding strand, and complete methylation of both strands occurs only after the gene has been silenced. The results of the study indicate that establishment of the de novo methylation pattern involves strand-specificity and methylation spreading. IntroductionDNA methylation in eukaryotes involves addition of a methyl group to the carbon 5 position of the cytosine ring. This reaction is catalyzed by DNA methyltransferase in the context of the sequence 5Ј-CG-3Ј, which is also referred to as a CpG dinucleotide. 1 Eukaryotic genomes are not methylated uniformly but contain methylated regions interspersed with unmethylated domains. 2 Approximately 70% to 80% of the CpG residues in most vertebrates are methylated. 3 In contrast to the rest of the genome, smaller regions of DNA called CpG islands are unmethylated and possess the expected CpG frequency. 4,5 During early development a dramatic reduction in methylation levels occurs in the preimplantation embryo. 6 This is followed by a wave of de novo methylation involving most CpG residues. However, CpG island-associated promoter regions are protected from methylation by mechanisms which remain unclear. 7 The methylation profile of genes in the adult is stable over many cell generations. Genomic methylation patterns are conserved after DNA replication by the DNA methyltransferase Dnmt1, which is the major maintenance methyltransferase. 8 Dnmt1 is recruited to replicating DNA to reproduce the methylation pattern of the parental strands in the daughter strands. 9 Inactivation of the mouse Dnmt1 gene by gene targeting resulted in extensive demethylation of all sequences examined. 10,11 However, ES cells completely lacking Dnmt1 were still capable of methylating retroviral DNA de novo. 11 The search for the de novo methyltransferases led to the discovery of Dnmt3a and Dnmt3b. 12 These were found to be essential for de novo methylation and for mouse development. 13 However, it remains unclear how de novo methylation patterns are established during development, over what time intervals these changes occur, or if this process involves any strand-or sequence-specifici...

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“…The significance of this degree of methylation is uncertain; however, regional DNA methylation can be influenced by Alu (44) or cis-acting sequences (45). Once de novo methylation has been "seeded," spreading of methylation may be possible (46).…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Profiling in Chronic Lymphocytic Leukemia Reveals Novel Methylation Targets

Rush

Raval

Funchain³

et al. 2004

Cancer Research

128

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CpG island methylation is an epigenetic alteration that contributes to tumorigenesis by transcriptional inactivation of genes. Little is known about the overall levels of CpG island methylation in chronic lymphocytic leukemia (CLL). To provide a baseline estimate of global aberrant methylation and identify target sequences for additional investigation, we performed Restriction Landmark Genomic Scanning on 10 CLL samples. Two methylation-sensitive landmark enzymes were used (NotI and AscI), allowing assessment of over 3000 CpG islands in each sample. Tumorderived Restriction Landmark Genomic Scanning profiles were compared with profiles from CD19-selected B cells from normal volunteers and matched normal neutrophils from 4 CLL patients. We found 2.5-8.1% (mean 4.8%) of the CpG islands in CLL samples were aberrantly methylated compared with controls, and the methylation events had a nonrandom distribution (P < 0.0001). Furthermore, we identified 193 aberrantly methylated sequences, of which 93% have CpG island characteristics and 90% have homology to genes or expressed sequences. One such gene, the G protein-coupled metabotropic glutamate receptor 7 (GRM7), possibly inhibits cyclic AMP signaling in the induction of apoptosis. Bisulfite sequencing of GRM7 confirmed extensive CpG island methylation, and treatment with 5-aza-2-deoxycytidine (decitabine) resulted in up-regulated expression of several genes in vitro with concurrent cellular depletion of DNMT1 protein. Our dual-enzyme global methylation study shows that CLL is characterized by widespread nonrandom CpG island methylation similar to other tumors and provides a panel of novel methylation targets that can be used in larger studies designed to assess impact on disease progression and survival.

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Spreading of methylation along DNA

Cited by 27 publications

References 19 publications

Integration and Expression Stability of Transgenes in Hybriding Transmission of Transgenic Rice Plants Produced by Particle Bombardment

Integration and Expression Stability of Transgenes in Hybriding Transmission of Transgenic Rice Plants Produced by Particle Bombardment

De novo methylation of an embryonic globin gene during normal development is strand specific and spreads from the proximal transcribed region

Epigenetic Profiling in Chronic Lymphocytic Leukemia Reveals Novel Methylation Targets

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