Lysine acetylation is gnarly and dynamic

This 2018 UC San Francisco cell review provided details of lysine acetylation:

“Lysine acetylation has moved from being a specialized mark on histones to a critical modification controlling cell fate, proliferation, and metabolism.

During the lifetime of a protein there are many points at which an acetyl group may be added to influence function. The dynamic interplay between the writers, erasers, and readers of acetylation regulates critical epigenomic and metabolic processes, in addition to other major cellular functions.

Acetylation sites are well conserved, in contrast to methylation, where species-specific differences exist.”

The review included a section on mitochondrial protein acetylation:

“Mitochondria have emerged as organelles in which acetylation is more prominent than phosphorylation and plays a key role in integrating metabolic cues with the bioenergetic equilibrium of the cell.

Increased mitochondrial protein acetylation is associated with physiological conditions that result in higher levels of acetyl-CoA (e.g., fasting, calorie restriction, high-fat diet, and ethanol intoxication).”

https://pubs.acs.org/doi/full/10.1021/acs.chemrev.7b00181 “Lysine Acetylation Goes Global: From Epigenetics to Metabolism and Therapeutics” (not freely available) Thanks to lead author Ibraheem Ali for providing a full copy.

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Epigenetic mechanisms of muscle memory

This 2018 UK human study detailed epigenetic muscle memory:

“We aimed to investigate an epigenetic memory of earlier hypertrophy in adult human skeletal muscle using a within measures design, by undertaking:

  1. Resistance exercise induced muscle growth (loading) [3 days a week for 7 weeks], followed by;
  2. Cessation of resistance exercise, to return muscle back towards baseline levels (unloading) [7 weeks], and;
  3. A subsequent later period of resistance exercise induced muscle hypertrophy (reloading) [3 days a week for 7 weeks].”

The findings were:

“Frequency of genome-wide hypomethylation is the largest after reloading induced hypertrophy where lean muscle mass is enhanced.

Hypomethylation is maintained from earlier load induced hypertrophy even during unloading where muscle mass returns back towards baseline, and is inversely associated with gene expression.

A single bout of acute resistance exercise evokes hypomethylation of genes that have enhanced gene expression in later reload induced hypertrophy.”


The study provided another example of how our bodies remember. It began with only eight male 27.6 ± 2.4 year-old subjects, though, and one of them dropped out.

See the discussion of a 2017 Netherlands human study in Are Underpowered Studies Ever Justified? with comments on studies with few subjects, such as:

“The problem occurs when people do small quantitative studies, but draw conclusions nonetheless, simply adding a disclaimer to the discussion (which they don’t put in the abstract, or the press release).”

“Underpowered studies may only be useful to check if the experiment works out wrt understanding instructions, do the programs run, etc, but not as much for testing and estimating effects.”

“The problem with underpowered studies is that all estimates can vary erratically between samples. Combined with the desire of many researchers (and universities’ press offices) to find sensational patterns, this means that evidence from underpowered studies is ‘asymmetrically’ likely to be considered more conclusive. As in, something that seems really cool will probably be considered more conclusive than something that’s disappointing. Highly powered studies don’t afford this flexibility.”

https://www.nature.com/articles/s41598-018-20287-3 “Human Skeletal Muscle Possesses an Epigenetic Memory of Hypertrophy”

Obtaining convictions with epigenetic statistics?

This 2018 Austrian review subject was forensic applications of epigenetic clock methodologies:

“The methylation-sensitive analysis of carefully selected DNA markers (CpG sites) has brought the most promising results by providing prediction accuracies of ±3–4 years, which can be comparable to, or even surpass those from, eyewitness reports. This mini-review puts recent developments in age estimation via (epi)genetic methods in the context of the requirements and goals of forensic genetics and highlights paths to follow in the future of forensic genomics.”


The point of forensic analysis techniques should be to find the truth about an individual. Doesn’t the principle of “All presumptive evidence of felony should be admitted cautiously; for the law holds it better that ten guilty persons escape, than that one innocent party suffer” still hold?

The methods’ limitations weren’t discussed. Here are some concepts not mentioned in the review:

1) Summary statistics that describe a group or population NEVER necessarily describe an individual member.

For an epigenetic clock methodology example, take a look at Figure 2A in Using an epigenetic clock to assess liver disease. 16 of the 18 individual age acceleration estimates of the control group subjects aren’t close to the median value!

2) The reviewer outlined basic DNA methylation analysis:

“The most commonly pursued approach for analysing CpG sites is sequence analysis of bisulfite-converted DNA, during which single-stranded genomic DNA is treated with sodium bisulfite that deaminates unmethylated cytosine to uracil, while methylated cytosine remains unaffected.

With increasing age, not only genome-wide DNA hypomethylation has been observed but also regional DNA hypermethylation of CpG islands.”

The basic limitation of this analysis wasn’t mentioned, but A study of DNA methylation and age said:

“Due to the methods applied in the present study, not all the effects of DNA methylation on gene expression could be detected; this limitation is also true for previously reported results.

The textbook case of DNA methylation regulating gene expression (the methylation of a promoter and silencing of a gene) remains undetected in many cases because in an array analysis, an unexpressed gene shows no signal that can be distinguished from background and is therefore typically omitted from the analysis.

3) Another omission was that the numbers and types of targets in the discussed DNA methylation technique were severely limited per The primary causes of individual differences in DNA methylation are environmental factors:

“A main limitation with studies using the Illumina 450 K array is that the platform only covers ~1.5 % of overall genomic CpGs, which are biased towards promoters and strongly underrepresented in distal regulatory elements, i.e., enhancers.

The reviewer didn’t provide convincing justifications for using gene expression profiling to obtain convictions. Was it too much to expect a mini-review to offer a balanced view of using epigenetic age estimation in forensic analyses?

https://www.karger.com/Article/FullText/486239 “Age Estimation with DNA: From Forensic DNA Fingerprinting to Forensic (Epi)Genomics: A Mini-Review”

A review of human pluripotent stem cell research

This 2018 Belgian review subject was human pluripotent stem cells (hPSCs):

“hPSCs are now starting to live up to the great expectations they created after their first derivation nearly twenty years ago. Indeed, the first results of clinical trials to treat macular degeneration are being published, and an increasing number of clinical or preclinical trials are being started for conditions such as spinal cord injury, diabetes and heart disease.

This imminent transition of pluripotent stem cells to the clinic has resulted in researchers and clinicians becoming acutely aware of the problems related to the genetic and epigenetic diversity of these cells, included acquired mutations.”

The review included a section on mitochondrial processes that impact the differentiation capacity of pluripotent stem cells, summarized by:

“From this overview, we also observe a more ample contribution of mtDNA in cell fate determination than is represented in many studies tackling the topic.

The transition from aerobic glycolysis to aerobic phosphorylation plays a vital role in cells’ ability to correctly proceed through differentiation, though the mtDNA is rarely evaluated.”

https://academic.oup.com/humupd/advance-article-abstract/doi/10.1093/humupd/dmx042/4825062?redirectedFrom=fulltext “Genetic and epigenetic factors which modulate differentiation propensity in human pluripotent stem cells” (not freely available) Thanks to lead author Alexander Keller for providing a copy.