Genetics

Epigenetic Memories

Written by Ezza Sohail

Epigenetics, a term that holds in itself a concept of regulated gene expression and gene switching i.e turning genes on and off according to requirement. Changes in the gene expression are due to the heritable factors and these factors or epigenetic tags do not bring any change in the sequence of DNA but they do transmit life time experiences among generations and that’s what we call as Epigenetic Memories. These memories help an organism to adopt itself for its better survival.

Epigenetic changes when occur in egg and sperm they are transmitted to the next generation. Some of the epigenetic changes that are inherited do not come from an egg or sperm rather they are because of the behavioral interaction with parents.

Epigenetic tags that act as main forces for driving gene regulation can be

  • DNA Methylation
  • Histone Modification
  • RNA Induced Epigenesis

DNA Methylation:

DNA is double helix structure that comprises of phosphate and sugar backbone along with four types of nucleotides. Adenine is always followed by Thymine and Cytosine is followed by Guanine also written as CpG whereas the p represents the phosphate bond pairing the two nucleotides. About more than half of the human genome consists of CpG sites also called as CpG Island. This CpG is of great importance because these are the only sites that can be epigenetically modified or methylated at cytosine residue. When there is more proportion of methylated CpG (hypermethylated) in a promoter the more repressed that gene is and if the promoter is hypomethylated the gene will be active.

In a zygote all of the genome is reprogrammed to ensure the totipotency of the zygote. But in the whole process of reprogramming the epigenetic markers from both the parents cannot be erased and they reappear. (1)

If the normal DNA Methylation pattern is altered in parents because of any environmental cues such as stress, drugs, or by the disturbed metabolic functions the changed DNA Methylation pattern is now passed onto the next generation. (2)

The first evidence of transgenerational transmission was provided by an experiment performed on rats. Rats were given an exposure of chemicals that disturbed their endocrine activity. The offspring resulted from generation F1-F4 had shown increased male infertility. (3)

Histone Modification:

Histone protein is an important component in the packaging of the DNA whereas the acetylation of histone is also an important aspect. Amino acids present in the histone tails receive acetyl group on them. Together the methylated DNA and DE acetylated histone are tightly packed and turn off the gene, while hypo methylated DNA and acetylated histone favor to turn on the gene. (4)

Inheritance of histone protein is still debatable; there has been two theories regarding histone inheritance. One theory suggests that histone modifications present on maternal chromosomes when they split these modifications are reduced. While other theory suggests that instead of histone modification an enzyme is passed onto the next generation and this enzyme is responsible for recreating histone modifications. Now to confirm either of the above two theories an experiment was performed in C. elegan worms. The eggs of these worms were modified and enzyme known as PCR2 was removed. PCR2 is responsible for the modifications on histone H3, a marker responsible for gene repression. These eggs were fertilized with wild type sperms containing PCR2 but sperms were unable to deliver their PCR2 enzyme resulting into a zygote with no histone modifying enzyme. With each cell division the histone H3 maker was becoming dull and at the age of 48 cells the marker was not visible. It implies that histone modifications are passed to the daughter chromosome.

Then they performed a reverse experiment in which the sperms do not contain any PCR2 while the eggs contain both the histone H3 marker and PCR2. Now this time the marker didn’t get dull because PCR2 was recreating the marker on daughter chromosome with each advanced cell division. Another important finding was that the marker was exactly created on the same location as it was on the parent chromosome. Hence the findings of the experiment suggest that histone modifications are transgenerational. (5)

RNA Induced Epigenesis:

Organisms had incorporated an astonishing feature of detecting the foreign nucleic acid in their bodies. For instance many viruses like RNA viruses when they invade an organism RNA silencing mechanism has been thought to be activated. This system had been very efficient to start silencing of the genes. This mechanism works by comparing the foreign sequence with the indigenous sequence and an epigenetic memory of that invader sequence has been made after silencing it. Now this epigenetic memory is transgenerational. This is how RNA silence a gene. (6)

Future Horizons:

The processes like Histone modification, DNA Methylation, and RNA silencing together results in the regulation of gene expression and formation of long term memory. These findings result in the birth of a new realm in science known as Neuroepigenetics. There has been now much evidence supporting learning and memory formation through epigenetics. It also helps in understanding the complex nature of higher level of organisms and how they have restored their capacity to learn and memorize information with continuous changes in their environment.

REFERENCES:

  1. Razin A, Riggs AD, (1980). DNA methylation and gene function. ;210:604–610
  2. Trerotola M, Relli V,  Simeone P, and Alberti S, (2015). Epigenetic inheritance and the missing heritability. Hum Genomics; 9(1): 17.
  3. Anway MD, Cupp AS, Uzumcu M, Skinner MK, (2005). Epigenetic transgenerational actions of endocrine disruptors and male fertility.Science,  308:1466–1469.
  4. Vaissie`re T, Sawan C, Herceg Z. (2008) Epigenetic interplay between Histone modifications and DNA methylation in gene silencing. Mutat Res, 659:40–48.
  5. J. Gaydos et al., “H3K27me and PRC2 transmit a memory of repression across generations and during development,”Science, 345:1515-18, 2014.
  6. University of Massachusetts Medical School. (2012, June 26). New role for RNAi discovered: Epigenetic memory may pass RNA silencing from one generation to the next.ScienceDaily.

 

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Ezza Sohail