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DNA Modification Mechanisms and Gene Activity during Development

Robin Holliday, +1 more
- 01 Jan 1996 - 
- Vol. 32, pp 639-645
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TLDR
In this paper, the authors suggest mechanisms that may explain the stability of dividing or non-dividing cells and also attempt to explain the ordered switching on or off of genes during development.
Abstract
It is generally accepted that the differentiated state of a given type of cell is associated with the activity of a particular set of genes, together with the total inactivity of those sets associated with the differentiation of other cell types. It is also clear that the differentiated state of dividing or nondividing cells is often extremely stable. In this article we suggest mechanisms that may account for this stability and that also attempt to explain the ordered switching on or off of genes during development. The phenotype of the organism depends on the genotype, and the genetic contribution from both parents is in almost all cases equal. Since the ultimate control of development resides in the genetic material, the actual program must be written in base sequences in the DNA. It is also clear that cytoplasmic components can have a powerful or overriding influence on genomic activity in particular cells, yet these cytoplasmic components are, of course, usually derived from the activity of genes at some earlier stage in development. A continual interaction between cytoplasmic enzymes and DNA sequences is an essential part of the model to be presented. Modification Enzymes In bacteria, enzymes exist which modify DNA by methylating adenine in the 6-position ( 1 ). These enzymes are extremely specific in their action; they modify bases at particular positions in short defined sequences of DNA, which, at least in some instances, form a palindrome. (A palindrome in DNA is an inverted duplication, with twofold rotational symmetry. The 3′ →...

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Functions of DNA methylation: islands, start sites, gene bodies and beyond

TL;DR: Improved genome-scale mapping of methylation allows us to evaluate DNA methylation in different genomic contexts: transcriptional start sites with or without CpG islands, in gene bodies, at regulatory elements and at repeat sequences.
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The molecular hallmarks of epigenetic control

TL;DR: A personal perspective on the development of epigenetics, from its historical origins to what is defined as 'the modern era of epigenetic research', is provided.
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Function and information content of DNA methylation

TL;DR: These observations indicate that the underlying DNA sequence largely accounts for local patterns of methylation, which is highly informative when studying gene regulation in normal and diseased cells, and it can potentially function as a biomarker.
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The DNA methyltransferase family: a versatile toolkit for epigenetic regulation

TL;DR: Analysis of molecular interactions and changes in gene copy numbers modulate the activity of DNMTs in diverse gene regulatory functions, including transcriptional silencing, transcriptional activation and post-transcriptional regulation by DNMT2-dependent tRNA methylation enables the DNMT family to function as a versatile toolkit for epigenetic regulation.
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DNA Methylation in Mammals

TL;DR: How DNA methylation serves as a cellular memory system and how it is dynamically regulated through the action of the DNA methyltransferase (DNMT) and ten eleven translocation (TET) enzymes is described.
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