Epigenetic Memory without NeoDarwinism



Epigenetics acts outside of neo-Darwinism. Neo-Darwinism is the theory of evolution that states that evolution occurs through the gradual accumulation of random mutations that are then passed on to offspring. Epigenetic changes, on the other hand, are changes in gene expression that do not involve changes in the DNA sequence.

The article "Inheritance of epigenetic transcriptional memory through read–write replication of a histone modification" by Brickner et al. investigates the molecular mechanisms by which histone modifications can be inherited from one cell generation to the next. Histone modifications are chemical changes to the proteins that package DNA into chromosomes. These modifications can alter the structure of chromatin, which is the complex of DNA and proteins that makes up chromosomes. Changes in chromatin structure can affect gene expression, the process by which genes are turned on and off.

Brickner et al. focused on the histone modification H3K4me2, which is associated with active gene transcription. They found that H3K4me2 can be inherited from one cell generation to the next through a process called read–write replication. In read–write replication, the histone modification is copied onto the newly synthesized DNA strand during DNA replication. This ensures that the same histone modification is present on both copies of the gene, even if the gene is turned off in the daughter cells.

Brickner et al. also found that H3K4me2 can be maintained through multiple cell divisions, even in the absence of the factors that originally established the modification. This suggests that H3K4me2 can be inherited epigenetically, meaning that it can be passed down from one cell generation to the next even in the absence of changes to the DNA sequence.

The findings of Brickner et al. have important implications for our understanding of epigenetics, the study of heritable changes in gene expression that do not involve changes to the DNA sequence. Epigenetic modifications are thought to play a role in a variety of biological processes, including development, aging, and disease. The study of how histone modifications are inherited could help us to better understand these processes and develop new treatments for diseases.

In addition to the implications for epigenetics, the study of Brickner et al. also has implications for our understanding of memory. Epigenetic modifications have been linked to memory formation and recall. The finding that H3K4me2 can be inherited epigenetically suggests that it may play a role in long-term memory. This is an area of active research, and further studies are needed to confirm this hypothesis.

Overall, the study of Brickner et al. provides new insights into the molecular mechanisms of epigenetic inheritance. This research could lead to a better understanding of the role of epigenetics in a variety of biological processes, including development, aging, and disease. It could also lead to the development of new treatments for diseases that are caused by epigenetic defects.

Here are some additional thoughts on the article:

  • The study of Brickner et al. highlights the importance of histone modifications in epigenetic inheritance. Histone modifications are relatively stable and can be inherited through multiple cell divisions. This makes them ideal for mediating long-term changes in gene expression, such as those that occur during development and memory formation.

  • The study also suggests that epigenetic inheritance is not a passive process. There are specific mechanisms that ensure that histone modifications are faithfully copied from one cell generation to the next. These mechanisms are not fully understood, but they are likely to involve the coordinated action of a variety of proteins.

  • The study of Brickner et al. has important implications for our understanding of human health. Epigenetic defects have been linked to a variety of diseases, including cancer, Alzheimer's disease, and autism spectrum disorder. Further research into the mechanisms of epigenetic inheritance could lead to the development of new treatments for these diseases.

Article Snippets

Inheritance of epigenetic transcriptional memory through read–write replication of a histone modification

Epigenetic transcriptional regulation frequently requires histone modifications. Some, but not all, of these modifications are able to template their own inheritance.

Recently, we found that the histone H3 lysine 4 dimethylation that is associated with this phenomenon plays a critical role in sustaining memory and, when factors critical for the establishment of memory are inactivated, can be stably maintained through multiple mitoses

This chromatin-mediated inheritance mechanism may involve a physical interaction between an H3K4me2 reader, SET3C, and an H3K4me2 writer, Spp1− COMPASS.

This is the first example of a chromatin-mediated inheritance of a mark that promotes transcription.

while the DNA sequence of the genome defines the phenotypic potential of an organism, that potential is realized through the regulation of gene expression, often through selective transcription.

Changes in transcription can be rapid and transient but, under certain circumstances, cells undergo long-term changes in gene expression that persist in the absence of the initiating stimulus.

Changes in transcription that are inherited through mitosis or meiosis are termed epigenetic transcriptional regulation.

How do cis-acting marks impact transcription?

Many regulators of transcription impact DNA accessibility by regulating nucleosome occupancy.

The heritability of DNA methylation and its requirement for the maintenance of certain epigenetic states suggests a general conceptual model for the inheritance of cis-acting information: following DNA replication, hemi-methylated CpG sites are recognized and remethylated on the complementary cytosine

a mechanism that both recognizes a cis-acting mark and stimulates its re-establishment might allow that mark to be faithfully inherited at that location.

Is there evidence that histone post-translational modifications are heritable? In other words, can cis-acting histone marks be perpetuated in the absence of trans-acting factors? Studies of the silencing of telomeres, centromeres, and special loci like the hidden mating type loci (HM) in flies and yeast suggested that histone modification-dependent transcriptional states are heritable in the absence of some of the trans-acting factors necessary for their establishment.

For histone modifications to be inherited, two conditions must be met. First, nucleosomes must be reincorporated into chromatin near their original location following DNA replication

the location of nucleosomes is quite stable over many cell divisions

This suggests that nucleosomes are preferentially reincorporated near their original location

Second, to facilitate the re-establishment of histone marks after DNA replication, the histone modifications on parental nucleosomes must be recognized (by a “reader”) and that must be coupled to the recruitment of the enzyme that modifies new nucleosomes (“writer”).

the best examples of heritable chromatin states are those associated with stable silencing.

Histone modifications associated with active transcription are, for the most part, not heritable; histone acetylation is unstable and nucleosomes in actively transcribed regions are not reincorporated faithfully at the same location through multiple cell divisions

However, modifications that reflect the previous transcription can be inherited.

Here, I highlight a phenomenon whereby a heritable histone modification over an inactive gene both reflects the previous expression and promotes future transcription

This mark (H3K4me2) is associated with both active and poised loci, although the molecular requirements and heritability in these two circumstances are different.

This phenomenon, called epigenetic transcriptional memory, was discovered in budding yeast84 but has since been observed in flies85 and human cells

The general features of this type of memory are the requirement for interaction with nuclear pore proteins, H3K4me2, and recruitment of poised RNAPII.

This type of memory persists through mitosis for between four and 15 cell divisions, depending on the system.



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