Patterns of DNA methylation are indistinguishable in different individuals over a wide range of human DNA sequences

Behn-Krappa, Annett; Hölker, Irmgard; Silva, Ute Sandaradura de; Doerfler, Walter

doi:10.1016/0888-7543(91)90095-v

Cited by 36 publications

(23 citation statements)

References 17 publications

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“…A total of 58 muscle samples were studied and all of them displayed identical EcoRI banding. This is in agreement with the presence of highly cell-type-specific patterns of DNA methylation in the human genome [18].…”

Section: Discussionsupporting

confidence: 76%

“…The mature tissue-specific patterns are the result of an interplay between demethylation and de novo methylation in the embryo [17]. Thus, finally differentiated somatic cells have a fixed pattern of methylation, constant among individuals [18], which is faithfully copied after replication through the strong preference of mammalian DNA methyltransferase for hemi-methylated DNA [19].…”

Section: Introductionmentioning

confidence: 99%

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De novo methylation causes a tissue-specific polymorphic EcoRI pattern at the human epidermal growth factor receptor gene

Arco

Izquierdo

1993

Biochemical Journal

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A novel restriction polymorphism, probably due to tissue-specific methylation, has been identified at the human epidermal-growthfactor-receptor (EGF-R) gene. DNA isolated from smooth muscle showed altered EcoRI restriction bands when hybridized with different fragments of the EGF-R cDNA. These bands were absent in brain or leucocyte DNA samples from the same individuals. Three restriction sites, partly resistant to cleavage by EcoRI, were characterized in muscle DNA which were not clustered but instead were scattered along the gene. The flanking sequences of one of these resistant EcoRI sites were determined. This specific EcoRI site was followed by a 3'-guanosine generating INTRODUCTION

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Section: Discussionsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

De novo methylation causes a tissue-specific polymorphic EcoRI pattern at the human epidermal growth factor receptor gene

Arco

Izquierdo

1993

Biochemical Journal

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“…About 300 bp upstream of the transcription start site of the human angiogenin gene, there is a very 5'-CG-3'-rich Alu element, Alu A ( Figure Sa, i), which is in the opposite orientation to the angiogenin gene (Kurachi et al, 1985 (Kochanek et al, 1990Behn-Krappa et al, 1991).…”

Section: Experimental Planmentioning

confidence: 99%

“…These patterns exhibit interindividual concordance in certain parts of the human genome (Kochanek et al, 1990Behn-Krappa et al, 1991) and can be related to levels of transcriptional activity (Doerfler, 1983(Doerfler, , 1992), or to replication or recombination in the genome. There are other segments that show interindividual differences in the extent of DNA methylation (Chandler et al, 1987;Silva and White, 1988).…”

Section: Introductionmentioning

confidence: 99%

DNA methylation in the Alu sequences of diploid and haploid primary human cells.

1993

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We have investigated DNA methylation in human Alu sequences, both in general and in specific Alu sequences associated with the genes for a1 globin, tissue plasminogen activator (tPA), adrenocorticotropic hormone (ACTH) and angiogenin. We studied DNAs from lymphocytes, granulocytes, brain, heart muscle and sperm, and from the human HeLa and KB cell lines by using cleavage with methylation-sensitive restriction enzymes combined with Southern blot hybridization and by using genomic sequencing. The results can be summarized as follows. (i) In differentiated primary human cells, Alu elements are often highly methylated even when they are in very 5'-CG-3'-rich regions. This finding is not consistent with the notion that hypermethylation would be a sufficient condition in itself for 5'-CG-3' sequences to undergo loss of 5-methyldeoxycytidine (5-mC) due to deamination and subsequent mutation. (ii) There are distinct differences in the levels of methylation in the specific Alu sequences. (iii) Alu elements in the DNA of haploid spermatozoa are much less methylated than in diploid cells. Preliminary data indicate that spermatozoa contain Alu-specific RNAs. (iv)The results of cell-free transcription experiments with Alu elements suggest that the in vitro transcription of Alu elements can be inhibited by 5'-CG-3' methylation. High levels of 5'-CG-3' methylation in Alu elements could contribute to their general transcriptional inactivity. (v) The patterns of methylation observed in the Alu elements and in the surrounding sequences are characterized by cell type specific interindividual concordance.

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“…By using the genomic sequencing technique (1, 2), we have shown that specific patterns of DNA methylation, in the human genes for tumor necrosis factors a and 8 (TNF-a and TNF-,B) (3) and in randomly selected sections of the human genome (4), are characterized by a high degree of interindividual concordance among people of different ethnic origins (3). Thus far, however, only a very small proportion of the human DNA has been analyzed.…”

mentioning

confidence: 99%

DNA methylation profiles in the human genes for tumor necrosis factors alpha and beta in subpopulations of leukocytes and in leukemias.

Kochanek

Radbruch

Tesch

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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The genomic sequencing technique has been applied to assess the state of methylation in the DNA from human leukocyte subpopulations from healthy individuals'and in the DNA from several individuals with myeloid or lymphatic leukemias or non-Hodgkin lymphomas. Leukocyte populations were purified by the high-gradient magnetic cell sorting' technique. In the human tumor necrosis factor a (TNF-a) gene segment between nucleotides 300 and 1150, the specific methylation profile in the DNA from human granulocytes and monocytes is maintained in three cases of myeloid leukemia. In one such case, all 5-methyl-2'-deoxycytidine residues' have been replaced by cytidine. In a chronic lymphatic T-cell leukemia, all 5-methyl-2'-deoxycytidine residues have been substituted by cytidine. In normal B lymphocytes, in two cases of chronic lymphatic B-cell leukemias and two cases of non-Hodgkin lymphomas, all 5'-CG-3' sequences in this gene segment are devoid of methylation. In the TNF-,B gene, DNA methylation is decreased in several examples of acute or chronic myeloid leukemias in comparison to normal human granulocytes or monocytes, whose DNA is almost completely methylated between nucleotides 700 and 900. In human T and B lymphocytes, the main producers of TNF-,B, in three instances of chronic lymphatic leukemias and two cases of non-Hodgkin Iymphomas, all 5'-CG-3' sequences are unmethylated in this region. The DNA from the human HeLa cell line is highly methylated at all 5'-CG-3' sequences in the TNF-a and -,f genes. The TNF-a gene is transcribed in the cells of one case of acute myeloid leukemia in which the analyzed region of the TNF-a gene is completely unmethylated. The TNF-8 gene is not transcribed in any of the malignant cells tested.Patterns of methylation in human DNA are specific for different cell types and can provide clues to states of genetic activities. By using the genomic sequencing technique (1, 2), we have shown that specific patterns of DNA methylation, in the human genes for tumor necrosis factors a and 8 (TNF-a and TNF-,B) (3) and in randomly selected sections of the human genome (4), are characterized by a high degree of interindividual concordance among people of different ethnic origins (3). Thus far, however, only a very small proportion of the human DNA has been analyzed. In other segments of the human genome, interindividual differences in methylation patterns have been reported (5, 6) and changes in human malignancies occur (7,8).We Fig. 1.Extraction of DNA and Genomic Sequencing. Nuclear DNA was extracted by the SDS/proteinase K/phenol method (11).The genomic sequencing method of Church and Gilbert (1) was applied with modifications (2, 12, 13). The TNF-a gene-containing fragment was excised from human DNA with Stu I and Bgl I and isolated by zone velocity sedimentation (3, 12). The DNA in the appropriate size fraction was recleaved with BstXI or Sty I (see Fig. 2a). Similarly, the TNF-,B gene was enriched, the initial cleavage being with Pvu II or BamHI followed by Hinfl (Fig. 3a). The presele...

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Patterns of DNA methylation are indistinguishable in different individuals over a wide range of human DNA sequences

Cited by 36 publications

References 17 publications

De novo methylation causes a tissue-specific polymorphic EcoRI pattern at the human epidermal growth factor receptor gene

De novo methylation causes a tissue-specific polymorphic EcoRI pattern at the human epidermal growth factor receptor gene

DNA methylation in the Alu sequences of diploid and haploid primary human cells.

DNA methylation profiles in the human genes for tumor necrosis factors alpha and beta in subpopulations of leukocytes and in leukemias.

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