Epigenetics

Epigenetics is defined as modifications in gene function that do not involve a change in the DNA base sequence.
The term was coined in 1942 by Conrad H. Waddington to explain phenotypic variation independent of genotype, particularly the differentiation of embryonic stem cells into distinct cell types.
Today, it's used to describe the control of gene expression independent of the underlying DNA sequence.
Important in many genetic traits and disorder.

The color of hydrangea flowers depends on the acidity of the soil, illustrating the influence of the environment on phenotype.
Monozygotic twins are not identical due to epigenetic factors.

DNA + Proteins = Chromatin
Epigenetic mechanisms are affected by factors such as development (in utero, childhood), environmental chemicals, drugs/pharmaceuticals, aging, and diet.

Nucleosomes consist of an octamer of core histones (H2A, H2B, H3, H4, each one x2), core DNA (approximately 147bp with 1.67 turns around the octamer), and linker DNA (~80bp) with histone H1.

The structure goes from DNA to nucleosomes ( $\approx$ 11nm) to 30nm fiber to higher order structures.
Histone modifications such as methylation, acetylation, phosphorylation, sumoylation, and ubiquitination, affect chromatin structure.

DNA methylation is the addition of a methyl group to DNA, typically at cytosine bases in CpG dinucleotides.
DNA methylation patterns are heritable during cell division and play a crucial role in gene silencing and maintaining chromatin structure.
5-methylcytosine is a common modified base in eukaryotic DNA.
DNA methylation is essential for normal development.

Histone modifications involve the addition or removal of chemical groups to histone proteins, affecting chromatin structure and gene expression.
Common modifications include acetylation, methylation, phosphorylation, and ubiquitination.
Histone acetylation is generally associated with increased gene expression, while histone methylation can either activate or repress gene expression depending on the specific lysine residue modified.

Non-coding RNAs (ncRNAs) are RNA molecules that do not encode proteins but play critical roles in gene regulation.
MicroRNAs (miRNAs) are small ncRNAs that regulate gene expression by binding to messenger RNAs (mRNAs) and inhibiting their translation or promoting their degradation.
Long non-coding RNAs (lncRNAs) are longer ncRNAs involved in various regulatory processes, including chromatin modification, transcription regulation, and RNA processing.

Genomic imprinting is a phenomenon in which certain genes are expressed in a parent-of-origin-specific manner.
Imprinted genes are typically marked by DNA methylation and histone modifications.
Imprinting plays a crucial role in development, and disruptions in imprinting can lead to various genetic disorders.

Alterations in DNA methylation patterns, histone modifications, and ncRNA expression have been implicated in various diseases, including cancer, cardiovascular disease, and neurological disorders.
Epigenetic modifications can contribute to tumorigenesis by altering the expression of tumor suppressor genes and oncogenes.
Epigenetic therapies, such as DNA methyltransferase inhibitors and histone deacetylase inhibitors, are being developed to treat cancer and other diseases.

Transgenerational epigenetic inheritance refers to the transmission of epigenetic information from one generation to the next.
Evidence suggests that environmental exposures, such as diet and stress, can induce epigenetic changes that are transmitted to subsequent generations.
Transgenerational epigenetic inheritance may have important implications for understanding the inheritance of complex traits and diseases.