Introducing Epigenetics: A Graphic Guide (Graphic Guides Book 0)

by Cath Ennis

In contrast, the paternal genome – which is tightly packaged with repressive protamine proteins, rather than histones (see here) – is activ...

These differences allow for parent-specific transcription of some genes, which is required for n...

The remethylation of the maternal and paternal genomes coincides with a major wave of cell differentiation. The locations of the new methyl groups become increasingly divergent in different cells. The initial divergence in epigenetic modification patterns stems from the first asymmetrical mitosis.

Once the cells reach full maturity, their epigenetic modification patterns (and therefore their gene transcription patterns, RNAs and proteins) stabilize and are copied through further rounds of mitosis. From this point on, the embryo focuses less on cell differentiation and increasingly on growth.

Ten to eleven weeks into the pregnancy, some of the maturing embryo’s cells undergo a second round of epigenetic reprogramming. This time, the maternal and paternal genomes demethylate simultaneously, but the paternal genome remethylates first. Again, this difference in timing allows for parentspecific gene transcription.

The cells that are reprogrammed twice are called primordial germ cells*, and will go on to produce the embryo’s own egg or sperm cells. The function of this second round of epigenetic reprogramming is to reset the epigenetic patterns of the next generation.

Many imprinted genes, which are transcribed from only one chromosome (see here), are involved in controlling cell growth and development. Imprinted genes therefore have to be tightly regulated in the embryo. Imprinted genes are associated with a piece of DNA called an imprint control region (ICR).

Methylated ICRs are recognized and bound by a protein called ZFP57, which recruits partners that protect these regions from demethylation during the first epigenetic reset in early embryonic development. ZFP57 is not present in primordial germ cells. The unprotected imprinted genes therefore do demethylate and remethylate during primordial germ cell development.

Kcnqlotl is only transcribed from the paternal chromosome, Cdknlc is only produced from the maternal chromosome.

X chromosome inactivation is the perfect demonstration of how different kinds of epigenetic regulation – DNA methylation, histone modifications and chromatin remodelling, all guided by a lncRNA – can cooperate to establish and maintain stable chromatin states.

One example of how childhood environments can have longterm epigenetic effects involves children who experience physical or emotional abuse, who often go on to suffer from lifelong poor health. Even people with no conscious memory of the abuse carry an increased risk of heart disease, cancer, substance abuse, depression and other conditions. Abuse causes permanent DNA methylation changes. The initial trigger is thought to be the stress response hormone cortisol, which abused children produce in large amounts.

exercise-induced changes in miRNA production and DNA methylation patterns. Exercise correlates with the silencing of genes that are involved in cell division and inflammation,

The ability of non-genetic factors to change epigenetic modification patterns helps to explain why identical twins aren’t truly identical. Siblings who share the same DNA sequence, but who accumulate increasingly different experiences and environmental exposures as they age, provide a unique opportunity to study the impact of epigenetics on human health.

twins are very epigenetically similar at birth, but their DNA methylation and especially their histone modification patterns diverge gradually over time.

truly unique: NASA’s 2015–16 experiment comparing identical twin astronauts, Scott and Mark Kelly, during and after Scott’s yearlong mission to the International Space Station. The results of NASA’s cosmic epigenetics research are highly anticipated.

Cells are particularly vulnerable to environmental exposures while they’re undergoing epigenetic reprogramming. A pregnant woman’s environment during the first week of embryonic development can create epigenetic changes with lifelong consequences for her child. Changes later in the pregnancy, around weeks ten to eleven, when the embryo’s primordial germ cells are developing can also affect her future grandchildren.

adolescent rats were exposed to tetrahydrocannabinol (THC), the active molecule in cannabis. After all the THC had cleared from the rats’ bodies, Hurd’s team allowed the test subjects to mate with untreated rats. The resulting pups were given to foster mothers with no previous THC exposure, in case the drug had affected the biological mothers’ parenting skills. When the pups matured, they were introduced to a system that required them to exert physical effort to self-administer heroin. Rats with a parent that had been exposed to THC were willing to put in more effort to obtain the drug.

Both male and female rats that were given THC as adolescents produced offspring that were predisposed to heroin addiction. The next generation – the grandchildren of the treated rats – also displayed altered patterns of behaviour. Yasmin Hurd’s original 2014 study found that the offspring of THC-treated rats have abnormal patterns of mRNA and protein production in their brain cells. Some of the affected proteins act as receptors for cannabis-based drugs, and are involved in compulsive behaviours and addiction.

During the harsh winter of 1944–5, the Nazis blocked all food imports to the Netherlands, causing a devastating famine. It’s estimated that 20,000 people died of starvation before food supplies returned to normal with the liberation of the Netherlands in May 1945.

people conceived during the famine (whose mothers were starving during early pregnancy) have an increased risk of obesity, diabetes and heart disease.

these risks correlate with reduced DNA methylation levels in imprinted genes that are involved in metabolism.

Children whose mothers first experienced starvation later in pregnancy weren’t affected in the same way, suggesting that earlier stage embryos are more vulnerable to...

the health effects of the famine persist in the survivors’ grandchildren.

One of the key findings of the Överkalix study concerns sex-specific patterns of disease risk in later generations: women who were in their mother’s womb during a period of famine passed on a higher risk of cardiovascular disease to their granddaughters, but not to their grandsons.

The Överkalix researchers also found sex-specific patterns of inheritance down the male line: men who had experienced a feast year between the ages of nine and twelve had grandsons – but not granddaughters – with shorter-than-average lifespans. Conversely, a period of famine in the same pre-puberty years resulted in healthier grandsons with longer lifespans.

Sperm precursor cells are differentiating and maturing in the years just before puberty, and thus might be vulnerable to epigenetic changes induced by the environment.

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Researchers have found correlations between certain traits that are thought to be affected by epigenetic inheritance and DNA methylation changes in specific genes, but this doesn’t necessarily mean that the two phenomena are directly related.

histone methylation can be inherited by the next generation. Strome’s study was performed in worms,

traumatic stress and obesity, respectively, can alter the repertoire of small RNAs in mouse sperm cells.

RNA-based mechanisms are also involved in human inheritance.

When everything works as it should, epigenetic modifications help to establish and maintain the patterns of gene activation and protein production that are necessary for normal embryonic development and for the continued functions of our cells throughout our lifespans.

Epigenetic drift causes different changes in each cell and each individual, but follows predictable general patterns. A few genes accumulate higher levels of DNA methylation over time, but the overall pattern is that the total amount of DNA methylation slowly diminishes as we age.

DNA methylation patterns are generally reversed in tumours. Regions that are usually methylated in normal cells often become reactivated (demethylated) in cancer cells.

Epigenetic regulator mutations are particularly common in blood cancers. For example, a single base change to the EZH2 gene is characteristic of several types of lymphoma.

histone deacetylase (HDAC) inhibitors prevent the removal of acetyl groups from histone tails.

DNA methyltransferase inhibitors are also being developed. The stable heritability of DNA methylation patterns (see here) ensures that the drug’s effects will persist in the offspring of any cancer cells that survive the original treatment.

In 2006, Japanese stem cell biologist Shinya Yamanaka (b. 1962) published a new method for creating stem cells directly from mature adult cells.

induced pluripotent stem cells (iPS cells)*

The fast pace of discovery and broad applications of epigenetics make it an attractive field for early-career scientists, with lots of room to carve out a unique research niche.

The International Human Epigenome Consortium (IHEC)

Methylation modifies mRNA stability, which in turn determines the abundance of the corresponding protein.

American computer scientist Yaniv Erlich to demonstrate in 2013 that it’s possible to infer the surnames of some donors from parts of their DNA sequence alone.

Codon: A sequence of three consecutive bases in an mRNA strand. Each codon specifies a single amino acid, although some amino acids are encoded by multiple codons.

CpG island: A cluster of CpGs (a C base adjacent to a G base, linked by a phosphate group, p) close to the transcription start site of a gene. The 70% of genes that have a CpG island are generally more active than the 30% that lack such structures.

Primordial germ cells: The cells within the developing embryo that, after cell differentiation, produce the egg or sperm cells.

Recombination: A process by which, prior to the first cell division during meiosis, the parents’ maternally- and paternally-derived chromosomes swap pieces of DNA, resulting in a hybrid chromosome which is passed to the resulting egg or sperm cell.

https://www.coursera.org/course/epigenetics: Online course. Requires an understanding of the basics of genetics.