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- Epigenetic Microenvironment Awakes Genes

The tissues of multicellular organisms are genetically homogeneous but phenotypically heterogeneous.  This phenomenon is due to the unusual variable expressivity of characters in the absence of genetic heterogeneity.  The variation in the expressivity of a character must have been due to the conditioning imparted during development and retained through mitosis.  The stable phenotypic alterations resulted due to conditioning without involving a change in DNA code of an allele is said to be “epigenetics” as both alleles and the conditioning factors are together heritable wherein no mutation is involved.  However, this phenomenon is unusually distinct from the maturation of B-cells whose genome undergoes hyper-somatic mutations to specialize for the secretion of a customized assembled immunoglobulin as per the prompting of T-helper cell.  At times, the extent to which environmental factors condition epigenetic responses is somewhat labile culminating in phenotypic mosaicism (variegation) among tissues and cells.  Thus, the epigenetic factors determine the variable expressivity of alleles and biased expressivity (imprinting) of either paternal or maternal alleles in the progeny. 


In 19th Century, Casper Friedrich Wolff introduced the term “epigenesis” to comprehend the mysterious workings of Nature that awakes the structures to form de novo from the apparent homogeneous (structureless) mass of a zygote (9).  The jargon of epigenesis is further brought into limelight through one of the branches of biology viz., Developmental Biology, which deals with the causative features of embryonic development wherein it is elaborated as: the study of changes in gene function due to combinatorial factors that are heritable among the cells of an embryo without bringing alterations in the concerned gene sequence, which means that the factors other than DNA supplement in the process of Heredity.  Further, the heritable epigenetic changes are called ‘epimutations’.  B. McClintock observed one of the first epimutations in maize through transposon activity (10).  Demethylation of a tandem repeat in the promoter accompanied the ectopic expression of the late flowering gene, fwa in ddm1 plants and this resulted in a dominant epimutation (10).  Methylated genes in Neurospora crassa behaved as epimutant alleles wherein methylation – associated silencing of transcript elongation were shown in Neurospsora (10). The term epiallele also comes into vogue whose epigenetic factors are stable at least through transgenerations.   For example, the transgene (Tg-13 HBV – E36-pas) when inherited paternally is unmethylated but maternal transmission of the same transgene results in methylation and transcriptional silencing (11).  Thus, as envisaged by Jenuwein and Allis (12), the phenomenon of epigenesis implies a fundamental regulatory system beyond nucleotide sequence information of DNA emphasizing that Mendel’s alleles are more than just a DNA moiety.

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