Transgenerational epigenetic inheritance

Transgenerational epigenetic inheritance is the transmission of epigenetic markers and modifications from one generation to multiple subsequent generations without altering the primary structure of DNA.^[1] Thus, the regulation of genes via epigenetic mechanisms can be heritable; the amount of transcripts and proteins produced can be altered by inherited epigenetic changes. In order for epigenetic marks to be heritable, however, they must occur in the gametes in animals, but since plants lack a definitive germline and can propagate, epigenetic marks in any tissue can be heritable.^{[citation needed]}

It is important to note that the inheritance of epigenetic marks in the immediate generation is referred to as intergenerational inheritance.^[2] In male mice, the epigenetic signal is maintained through the F1 generation.^[3] In female mice, the epigenetic signal is maintained through the F2 generation as a result of the exposure of the germline in the womb.^[3] Many epigenetic signals are lost beyond the F2/F3 generation and are no longer inherited, because the subsequent generations were not exposed to the same environment as the parental generations.^[2] The signals that are maintained beyond the F2/F3 generation are referred to as transgenerational epigenetic inheritance (TEI), because initial environmental stimuli resulted in inheritance of epigenetic modifications.^[4] There are several mechanisms of TEI that have shown to affect germline reprogramming, such as transgenerational increases in susceptibility to diseases, mutations, and stress inheritance. During germline reprogramming and early embryogenesis in mice, methylation marks are removed to allow for development to commence, but the methylation mark is converted into hydroxymethyl-cytosine so that it is recognized and methylated once that area of the genome is no longer being used,^[5] which serves as a memory for that TEI mark. Therefore, under lab conditions, inherited methyl marks are removed and restored to ensure TEI still occurs. However, observing TEI in wild populations is still in its infancy, as laboratory studies allow for more tractable systems.^[6]

Environmental factors can induce the epigenetic marks (epigenetic tags) for some epigenetically influenced traits.^[1] These can include, but are not limited to, changes in temperature, resources availability, exposure to pollutants, chemicals, and endocrine disruptors.^[7] The dosage and exposure levels can affect the extent of the environmental factors' influence over the epigenome and its effect on later generations. The epigenetic marks can result in a wide range of effects, including minor phenotypic changes to complex diseases and disorders.^[7] The complex cell signaling pathways of multicellular organisms such as plants and humans can make understanding the mechanisms of this inherited process very difficult.^[8]