There are several factors and mechanisms affecting transgenerational epigenetic inheritance
In recent days we have seen several articles about transgenerational epigenetic inheritance. Typically these articles are based on research made by population geneticists who try to belittle the importance of epigenetic inheritance. Here's a couple of examples:https://www.cell.com/cell/fulltext/S0092-8674(18)31255-8#.W-VG7yzrTNw.twitter
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065375/
Serious science takes account of all known factors and mechanisms regarding epigenetic inheritance. This is a much better paper:
https://humgenomics.biomedcentral.com/articles/10.1186/s40246-015-0041-3
Excerpt from abstract: "Genome-wide association studies of complex physiological traits and diseases consistently found that associated genetic factors, such as allelic polymorphisms or DNA mutations, only explained a minority of the expected heritable fraction. This discrepancy is known as “missing heritability”, and its underlying factors and molecular mechanisms are not established. Epigenetic programs may account for a significant fraction of the “missing heritability.” Epigenetic modifications, such as DNA methylation and chromatin assembly states, reflect the high plasticity of the genome and contribute to stably alter gene expression without modifying genomic DNA sequences.
Consistent components of complex traits, such as those linked to human stature/height, fertility, and food metabolism or to hereditary defects, have been shown to respond to environmental or nutritional condition and to be epigenetically inherited. The knowledge acquired from epigenetic genome reprogramming during development, stem cell differentiation/de-differentiation, and model organisms is today shedding light on the mechanisms of (a) mitotic inheritance of epigenetic traits from cell to cell, (b) meiotic epigenetic inheritance from generation to generation, and (c) true transgenerational inheritance. Such mechanisms have been shown to include incomplete erasure of DNA methylation, parental effects, transmission of distinct RNA types (mRNA, non-coding RNA, miRNA, siRNA, piRNA), and persistence of subsets of histone marks."
Serious science takes account of all known factors and mechanisms regarding epigenetic inheritance. This is a much better paper:
https://humgenomics.biomedcentral.com/articles/10.1186/s40246-015-0041-3
Consistent components of complex traits, such as those linked to human stature/height, fertility, and food metabolism or to hereditary defects, have been shown to respond to environmental or nutritional condition and to be epigenetically inherited. The knowledge acquired from epigenetic genome reprogramming during development, stem cell differentiation/de-differentiation, and model organisms is today shedding light on the mechanisms of (a) mitotic inheritance of epigenetic traits from cell to cell, (b) meiotic epigenetic inheritance from generation to generation, and (c) true transgenerational inheritance. Such mechanisms have been shown to include incomplete erasure of DNA methylation, parental effects, transmission of distinct RNA types (mRNA, non-coding RNA, miRNA, siRNA, piRNA), and persistence of subsets of histone marks."
My comment: So, modern science is aware of at least 25 different molecular mechanisms affecting transgenerational epigenetic inheritance. These are:
Especially the role of non coding RNA molecules in the epigenetic inheritance is understudied. Serious scientists are focusing on histone epigenetic markers because they seem to be a biological database having a strong influence on how DNA is read and transcribed. We have seen several articles about switching genes on or off but this is too narrow view about how DNA is used by cellular mechanisms. Reading and transcribing of DNA is just the first step in making a functional product, an RNA molecule.
Here's a good example of how epigenetic markers, especially the histone code is affecting one of the most significant human traits, the height:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208652/
Category
|
Molecular mechanism
|
DNA
sequence-invariant heritable traits
|
DNA
methylation/histone post-translational modifications
|
DNA methylation
maintenance across cell division cycles
|
Hemimethylated
DNA-guided, DNMT1-mediated CpG methylation pattern maintenance
|
DNA demethylation
|
Passive DNA demethylation
|
-5-mC to 5-hmC conversion
|
|
Active DNA demethylation
|
|
-Glycosylase-mediated base removal and
base excision repair mechanisms
|
|
Histone code
|
Condensed chromatin
|
-HAT inactivation
|
|
-HMT activation
|
|
Relaxed chromatin
|
|
-HAT activation
|
|
-HMT inactivation
|
|
Epigenetic
modulation of mother-to-fetus transmission
|
Maternal nutrition status
|
Maternal exposure to
environmental toxins and food contaminants
|
|
-BPA
|
|
-Phthalates
|
|
-Dioxins
|
|
-Tobacco smoke
|
|
Cell differentiation
and body development
|
Epigenetic signature reprogramming
|
-Erasure/reprogramming in the zygote
(mitotic transmission)
|
|
-Erasure/reprogramming in PGCs (meiotic
transmission)
|
|
Gamete-carried transmission
|
|
-DNA methylation profiles in sperm and
oocytes
|
|
-H3K4 and H3K27 histone methylation in
sperm cells
|
|
-RNA molecules carried by sperm cells
(mRNA, non-coding RNA, miRNA, siRNA, piRNA)
|
|
Stem cell reprogramming
|
Epigenetic signature
of induced pluripotency
|
-Decreased TETs/decreased
hydroxymethylation at ES gene promoters
|
|
-Reprogramming-resistant regions enriched
for H3K9me3
|
Especially the role of non coding RNA molecules in the epigenetic inheritance is understudied. Serious scientists are focusing on histone epigenetic markers because they seem to be a biological database having a strong influence on how DNA is read and transcribed. We have seen several articles about switching genes on or off but this is too narrow view about how DNA is used by cellular mechanisms. Reading and transcribing of DNA is just the first step in making a functional product, an RNA molecule.
 |
| Major biological functions of lncRNAs in epigenetic, transcriptional, and posttranscriptional regulation. (a) DNA methylation, (b) genomic imprinting, (c) chromatin remodeling, (d) histone modifications, (e) transcriptional regulation, and (f) posttranscriptional regulation. |
Here's a good example of how epigenetic markers, especially the histone code is affecting one of the most significant human traits, the height:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208652/
Modern scientists know that histone code is established during embryonic development and non coding RNA molecules have a strong impact on this process. According to NONCODE, there are over 167,000 different long non coding RNAs (lncRNAs) functioning in a human body. The number of different lncRNAs in human sperm is also up to several thousands, probably tens of thousands. They are carried by extracellular vesicles such as exosomes and they have a significant role in establishing the histone code that mostly determines organismal characteristics and traits. DNA methylation profiles are also meaningful regarding epigenetic inheritance but most of them are erased during embryonic development. Here's a great study over histone code and long non coding RNA molecules:
http://tcr.amegroups.com/article/view/15283/html
http://tcr.amegroups.com/article/view/15283/html
So, before claiming that transgenerational epigenetic inheritance is just a minor contributor regarding inheritance, scientists should carefully investigate these several epigenetic factors and mechanisms, especially the role of histone code and non coding RNA molecules.
