D2.2.7 Epigenetic inheritance through heritable changes to gene expression Notes

Epigenetic Tags Are Chemical Modifications That Determine Which Genes Are Active or Silent

1. Imagine a library where some books are locked away, while others are open for reading.
2. The books represent genes, and the locks are epigenetic tags.
3. Unlike changes to the DNA sequence, these tags can be influenced by the environment and sometimes passed on to future generations.
4. Two primary mechanisms regulate these tags: DNA methylation and histone modification.

Key Mechanisms of Epigenetic Regulation

1. DNA Methylation

1. DNA methylation involves the addition of a methyl group ($CH_3$) to cytosine bases in DNA, typically occurring in CpG islands near promoter regions.
2. This process silences genes by:
   1. Blocking Transcription Factors and RNA Polymerase: Methylation prevents these molecules from binding to the promoter, halting transcription of the downstream gene.
   2. Recruiting Repressor Proteins: Methylated DNA attracts proteins that compact chromatin, making it inaccessible for transcription.

2. Histone Modifications

1. Chemical changes (e.g., acetylation, methylation) to histone proteins.
2. Modify how tightly DNA is wrapped around histones, affecting gene accessibility.
   1. Acetylation: Loosens chromatin to activate transcription.
   2. Methylation: Can activate or repress transcription depending on the site.

Epigenetic Tags Are Inherited During Mitosis and Meiosis

1. Inheritance During Mitosis

1. When cells divide, their epigenetic patterns are passed to daughter cells.
2. This ensures that specialized cells, like muscle or nerve cells, maintain their unique functions over an organism's lifetime.

2. Inheritance During Meiosis

1. Most epigenetic tags are erased during the formation of sperm and eggs, a process that resets the genome for the next generation.
2. However, some tags persist, allowing transgenerational epigenetic inheritance.

Limitations and Challenges of Epigenetic Inheritance

1. Reversibility: Unlike DNA mutations, epigenetic changes are often reversible, which may limit their long-term impact.
2. Incomplete Erasure: While most tags are erased during gamete formation, some escape this process, leading to unpredictable transgenerational effects.
3. Complexity: The exact mechanisms that determine which tags persist during inheritance remain poorly understood, making it a challenging field of study.

Real-World Applications

1. Medicine: Epigenetic therapies target abnormal DNA methylation and histone modifications to treat diseases like cancer and neurological disorders.
2. Agriculture: Understanding epigenetic inheritance can aid in developing crops that are more resilient to environmental stressors, such as drought or salinity.

Reflection and Review

1. Epigenetic inheritance highlights the intricate relationship between genetics and the environment.
2. It shows how phenotypic changes, influenced by epigenetic tags like DNA methylation and histone modifications, can be passed to daughter cells and, in some cases, offspring.
3. While much is still unknown, this field offers groundbreaking potential for understanding biology, improving human health, and addressing global challenges.