Transgenerational epigenetic inheritance

"Intergenerational" vs "transgenerational" 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.[2]

The inheritance of epigenetic marks in the immediate generation is referred to as intergenerational inheritance.[3] In male mice, the epigenetic signal is maintained through the F1 generation.[4] In female mice, the epigenetic signal is maintained through the F2 generation as a result of the exposure of the germline in the womb.[4] 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.[3] 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.[5] 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,[6] 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.[7]

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.[8] 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.[8] The complex cell signaling pathways of multicellular organisms such as plants and humans can make understanding the mechanisms of this inherited process very difficult.[9]

  1. ^ a b Moore, David Scott (2015). The developing genome : an introduction to behavioral epigenetics. Oxford. ISBN 978-0-19-992235-2. OCLC 899240120.{{cite book}}: CS1 maint: location missing publisher (link)
  2. ^ Pikaard, Craig S.; Mittelsten Scheid, Ortrun (December 2014). "Epigenetic Regulation in Plants". Cold Spring Harbor Perspectives in Biology. 6 (12): a019315. doi:10.1101/cshperspect.a019315. ISSN 1943-0264. PMC 4292151. PMID 25452385.
  3. ^ a b Heard, Edith; Martienssen, Robert A. (2014-03-27). "Transgenerational Epigenetic Inheritance: Myths and Mechanisms". Cell. 157 (1): 95–109. doi:10.1016/j.cell.2014.02.045. ISSN 0092-8674. PMC 4020004. PMID 24679529.
  4. ^ a b Fitz-James, Maximilian H.; Cavalli, Giacomo (June 2022). "Molecular mechanisms of transgenerational epigenetic inheritance". Nature Reviews Genetics. 23 (6): 325–341. doi:10.1038/s41576-021-00438-5. ISSN 1471-0064. PMID 34983971. S2CID 245703043.
  5. ^ Fitz-James, Maximilian H.; Cavalli, Giacomo (June 2022). "Molecular mechanisms of transgenerational epigenetic inheritance". Nature Reviews Genetics. 23 (6): 325–341. doi:10.1038/s41576-021-00438-5. ISSN 1471-0056. PMID 34983971. S2CID 245703043.
  6. ^ Iqbal, Khursheed; Jin, Seung-Gi; Pfeifer, Gerd P.; Szabó, Piroska E. (March 2011). "Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine". Proceedings of the National Academy of Sciences. 108 (9): 3642–3647. Bibcode:2011PNAS..108.3642I. doi:10.1073/pnas.1014033108. ISSN 0027-8424. PMC 3048122. PMID 21321204.
  7. ^ Husby, Arild (2022-02-09). "Wild epigenetics: insights from epigenetic studies on natural populations". Proceedings of the Royal Society B: Biological Sciences. 289 (1968): 20211633. doi:10.1098/rspb.2021.1633. ISSN 0962-8452. PMC 8826306. PMID 35135348.
  8. ^ a b Ho, Shuk-Mei; Johnson, Abby; Tarapore, Pheruza; Janakiram, Vinothini; Zhang, Xiang; Leung, Yuet-Kin (December 2012). "Environmental Epigenetics and Its Implication on Disease Risk and Health Outcomes". ILAR Journal. 53 (3–4): 289–305. doi:10.1093/ilar.53.3-4.289. ISSN 1084-2020. PMC 4021822. PMID 23744968.
  9. ^ Emmanuel, DROUET (2016-09-30). "Epigenetics: How the environment influences our genes". Encyclopedia of the Environment. Retrieved 2023-02-22.