Epigenetics and Its Mechanisms

Study Notes

The study of heritable changes in gene expression that occur without alterations to the underlying DNA sequence.
It encompasses the mechanisms that control gene activity in response to environmental or developmental cues.

The study of the complete set of epigenetic modifications across the entire genome of an organism.
It explores how these modifications influence cellular function, development, and disease.

An environmental factor that can influence the epigenome, triggering epigenetic changes.
Examples include diet, stress, and exposure to toxins.

A molecular entity that directly initiates epigenetic modifications, such as DNA-binding proteins and non-coding RNAs (ncRNAs).
They serve as the initial trigger for altering gene expression.

A mechanism that perpetuates and maintains epigenetic modifications over time.
Examples include DNA methylation, histone modifications, and chromatin remodeling.

DNA-Binding Proteins: Specific proteins that recognize and bind to DNA sequences, influencing gene expression.
Non-Coding RNAs (ncRNAs): RNA molecules that do not code for proteins but play regulatory roles.
Chromatin Remodeling: Processes that alter the structure and accessibility of chromatin, influencing gene activity.

DNA-binding proteins: Interact directly with specific DNA sequences, promoting or suppressing gene transcription.
ncRNAs: Interact with DNA or other RNA molecules to influence gene expression.
Example: Regulatory ncRNAs can guide the recruitment of chromatin-modifying complexes to specific genomic loci, leading to changes in histone modifications and gene activity.

DNA methylation: The addition of a methyl group to DNA bases, primarily cytosine, leading to gene silencing.
Histone modifications: Chemical modifications of histone proteins, such as methylation, phosphorylation, acetylation, ubiquitylation, and sumoylation, affecting chromatin structure and gene transcription.
Example: Acetylation of histone tails is typically associated with gene activation, while methylation can contribute to gene silencing.

Unequal expression of alleles (alternative forms of a gene) from a homologous chromosome pair observed due to epigenetic modifications.
This can occur through several mechanisms, including:
Somatic rearrangement: Genetic modifications within a cell lineage, such as certain immune cells.
Random allelic silencing: Stochastic inactivation of one allele, often observed in X chromosome inactivation.
Imprinting: Epigenetic modifications inherited from one parent that silence genes on the other parental chromosome, leading to parent-of-origin-specific gene expression.

A process in female mammals where one X chromosome is randomly inactivated in each cell, effectively silencing one allele.
This occurs through a cascade of epigenetic events initiated by the X-inactive specific transcript (XIST) gene, leading to the formation of a transcriptionally silent Barr body.
Biological Role: Ensures dosage compensation, balancing gene expression from the X chromosome between females and males.

Epigenetic modifications play a critical role in human health, contributing to the development of various diseases.
Aberrant epigenetic patterns, such as altered DNA methylation or histone modifications, are associated with conditions like cancer, neurodevelopmental disorders, and cardiovascular diseases.
Epigenomics is a powerful tool to understand the underlying mechanisms and explore potential therapeutic strategies for these diseases.