The sequence specificity of a mammalian DNA methylase

Browne, Michael; Turnbull, J. F.; McKay, E.L.; Adams, Roger; Burdon, Roy H.

doi:10.1093/nar/4.4.1039

Cited by 30 publications

(7 citation statements)

References 12 publications

(3 reference statements)

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“…However, epigenetic control of gene expression by DNA methylation gives rise to a fifth base in DNA, 5-methyl-cytosine (5-MeC). Methylation of cytosine is found almost exclusively at CpG di-nucleotides in animals [23]. These CpG di-nucleotides occur at an unusual frequency in the human genome, approximately one-fifth of their expected value.…”

Section: Dna Methylationmentioning

confidence: 99%

An epigenetic perspective on the free radical theory of development

Hitchler

Domann

2007

Free Radical Biology and Medicine

218

158

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The development of organisms requires concerted changes in gene activity. The free radical theory of development proposes that oxygen serves as a morphogen to educe development by influencing the production of metabolic oxidants such as free radicals and reactive oxygen species. One of the central tenets of this theory is that these metabolic oxidants influence development by altering the antioxidant capacity of cells by changing their production of glutathione (GSH). Here we extend on these principles by linking GSH production and oxygen sensing in the control of gene expression to establish the epigenotype of cells during development. We prescribe this novel role to GSH and oxygen during development because these metabolites influence the activity of enzymes responsible for initiating and perpetuating epigenetic control of gene expression. Increased GSH production influences epigenetic processes including DNA and histone methylation by limiting the availability of S-adenosylmethionine, the cofactor utilized during epigenetic control of gene expression by DNA and histone methyltransferases. Moreover, the recent discovery of histone demethylases that require oxygen as a cofactor directly links epigenetic processes to oxygen gradients during development.

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Section: Dna Methylationmentioning

confidence: 99%

An epigenetic perspective on the free radical theory of development

Hitchler

Domann

2007

Free Radical Biology and Medicine

218

158

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“…DNA is methylated almost exclusively at cytosines that are part of a CpG di-nucleotides [29]. CpG di-nucleotides are unusual for two reasons.…”

Section: Dna Methylationmentioning

confidence: 99%

Metabolic defects provide a spark for the epigenetic switch in cancer

Hitchler

Domann

2009

Free Radical Biology and Medicine

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Cancer is a pathology that is associated with aberrant gene expression and an altered metabolism. While changes in gene expression have historically been attributed to mutations, it has become apparent that epigenetic processes also play a critical role in controlling gene expression during carcinogenesis. Global changes in epigenetic processes including DNA methylation and histone modifications have been observed in cancer. These epigenetic alterations can aberrantly silence or activate gene expression during the formation of cancer; however, the process leading to this epigenetic switch in cancer remains unknown. Carcinogenesis is also associated with metabolic defects that increase mitochondrially derived reactive oxygen species, create an atypical redox state, and change the fundamental means by which cells produce energy. Here, we summarize the influence of these metabolic defects on epigenetic processes. Metabolic defects affect epigenetic enzymes by limiting availability of the cofactors like S-adenosylmethionine. Increased production of reactive oxygen species alters DNA methylation and histone modifications in tumor cells by oxidizing DNMTs and HMTs, or through direct oxidation of nucleotide bases. Lastly, the Warburg effect and increased glutamine consumption in cancer influences histone acetylation and methylation by affecting the activity of sirtuins and histone demethylases.

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“…Methylated, covalently bound oligonucleotide was puri®ed away from free DNA by electrophoresis in SDS/polyacrylamide gels and electrophoretic transfer to nitrocellulose membranes as shown in Figures 2 to 4, and the nonFdC strand was released from the complex by heating to 100 C. The DNA was then ampli®ed by PCR and the products cloned and sequenced to determine whether Dnmt1 preferentially interacts with speci®c sequences within the mixture of FdC oligonucleotides. Methyl-transfer assays with oligonucleotides of unique sequence had suggested that crude preparations of partially proteolyzed DNA methyltransferases do display strong sequence preferences (Browne et al, 1977;Bolden et al, 1986a,b).…”

Section: The Sequence-specificity Of Dnmt1mentioning

confidence: 99%