In 2007 Nature devoted a whole special topics issue to epigenetics. Here is a good article:
Nature 447, 396-398 (24 May 2007) | doi:10.1038/nature05913; Published online 23 May 2007
Introduction
Perceptions of epigenetics
Adrian Bird1
Top of pageAbstract
Geneticists study the gene; however, for epigeneticists, there is no obvious 'epigene'. Nevertheless, during the past year, more than 2,500 articles, numerous scientific meetings and a new journal were devoted to the subject of epigenetics. It encompasses some of the most exciting contemporary biology and is portrayed by the popular press as a revolutionary new science " an antidote to the idea that we are hard-wired by our genes. So what is epigenetics?
There has always been a place in biology for words that have different meanings for different people. Epigenetics is an extreme case, because it has several meanings with independent roots. To Conrad Waddington, it was the study of epigenesis: that is, how genotypes give rise to phenotypes during development1. By contrast, Arthur Riggs and colleagues defined epigenetics as the study of mitotically and/or meiotically heritable changes in gene function that cannot be explained by changes in DNA sequence2: in other words, inheritance, but not as we know it. These definitions differ markedly, although they are often conflated as though they refer to a single phenomenon. Waddington's term encompasses the activity of all developmental biologists who study how gene activity during development causes the phenotype to emerge, but it suffers from the disadvantage that developmental biologists themselves rarely, if ever, use this word to describe their field. In this sense, the usage is obsolete. The definition put forward by Riggs and colleagues tells us what epigenetics is not (inheritance of mutational changes), leaving open what kinds of mechanism are at work. In this article, I give examples of how epigenetic phenomena are studied and interpreted, and I propose a revised definition that embodies contemporary usage of the word.[cut]
Epigenetics and inheritance
Should heritability be mandatory in a contemporary view of epigenetics? The requirement that epigenetic characters should be transmissible through mitosis or meiosis has the virtue of clarity but can be a liability. To explain why, it is necessary to introduce a third, somewhat informal, 'definition' of epigenetics that has crept into widespread use. This incarnation of epigenetics encompasses the biology of chromatin, including the complex language of chromatin marks (see page 407), the transcriptional effects of RNA interference (see page 399) and, for good measure, the effects of the higher-order structure of chromosomes and the nucleus (see page 413). The attraction of this usage is that it brackets together some of the most exciting contemporary work in biology. Its drawback is that it does not sit easily with the prevailing textbook definitions. One reason for this is that many chromatin marks are short-lived. For example, phosphorylation of the variant histone H2AX (also known as H2AFX) after a double-strand break11 would qualify as an epigenetic mark under the emerging definition, but it is too transient to qualify as a heritable epigenetic mark (Fig. 2). Histone modifications associated with transcription are also ambiguous with respect to heritability. On the one hand, DNA methylation affects histone acetylation and histone methylation, so these modifications can be viewed as heritably epigenetic, albeit indirectly12. On the other hand, these histone marks can also result from events that seem to involve neither DNA methylation nor Polycomb group proteins, and the marks are not necessarily transmissible between generations. Therefore, a single histone modification could, in principle, be rated as either epigenetic or not epigenetic according to the heritability credentials of its origin. Such a complicated classification system would have limited utility.
Refining a definition
Given that there are several existing definitions of epigenetics, it might be felt that another is the last thing we need. Conversely, there might be a place for a view of epigenetics that keeps the sense of the prevailing usages but avoids the constraints imposed by stringently requiring heritability. The following could be a unifying definition of epigenetic events: the structural adaptation of chromosomal regions so as to register, signal or perpetuate altered activity states. This definition is inclusive of chromosomal marks, because transient modifications associated with both DNA repair or cell-cycle phases and stable changes maintained across multiple cell generations qualify. It focuses on chromosomes and genes, implicitly excluding potential three-dimensional architectural templating of membrane systems and prions, except when these impinge on chromosome function. Also included is the exciting possibility that epigenetic processes are buffers of genetic variation, pending an epigenetic (or mutational) change of state that leads an identical combination of genes to produce a different developmental outcome17.
An implicit feature of this proposed definition is that it portrays epigenetic marks as responsive, not proactive. In other words, epigenetic systems of this kind would not, under normal circumstances, initiate a change of state at a particular locus but would register a change already imposed by other events. Such events could be, for example, the collision of DNA with ionizing radiation or a developmental switch in gene expression. It could be argued that the responsive nature of epigenetic processes is a unifying feature, because classic epigenetic systems such as the DNA methylation system and the Polycomb/Trithorax systems seem to respond to previous switches in gene activity in this way. Therefore, their sophisticated feature is the ability, in the 'darkness' of the nucleus, to sense and mark changes in the chromosomal status. For example, transcriptional activation through sequence-specific DNA-binding proteins brings in histone acetyltransferases, which then epigenetically adapt the promoter region for transcription (for histone acetyl groups, although ephemeral, would now be epigenetic). Similarly, elongating polymerases carry enzymes that restrain the spurious transcriptional initiation that might arise within the temporarily disrupted chromatin of an active gene. Without such epigenetic mechanisms, hard-won changes in genetic programming could be dissipated and lost; transient disruptions of chromosomal organization might go uncompensated; and DNA damage might escape repair.
From another paper:
Epigenetic spillover across generations
Many of the epigenetic marks that are inherited and acquired by germ cells are therefore erased in PGCs and in early embryos, making way for new generations to develop and grow into adults purely on the basis of their genetic make-up. However, it also seems that epigenetic information can spill over to the next generation. The ability of somatic cells in the offspring to inherit the methylation of imprinted genes from parental germ cells is a mechanistic example of this (Fig. 4c). Another important example of spillover is inheritance of the epigenetic states conferred on some genes by adjacent insertion of IAPs. This can alter the expression of the endogenous genes; however, more importantly, the epigenetic state of the IAP (that is, methylated or unmethylated) regulates the expression of the nearby gene61. Because IAPs seem generally resistant to reprogramming during PGC and pre-implantation development, the state of expression of the genes that are regulated by IAP insertion can be inherited across several generations. It is interesting to note that there is an example of epigenetic inheritance being maternally transmitted but not paternally transmitted (the agouti viable yellow epiallele in mice), and the methylation of the IAP in the sperm is, unusually, erased in the zygote in this case62. So epigenetic inheritance is 'broken' by erasure of methylation of the paternal genome after fertilization.
Reik, Wolf Nature 447, 425-432 (24 May 2007) | doi:10.1038/nature05918; Published online 23 May 2007
Stability and flexibility of epigenetic gene regulation in mammalian development
So, epigenetic changes are NOT always inherited. Only
sometimes.
Now, Im not even sure what your overall argument ABOUT this is. What are you trying to claim epigenetics do, or have done?
