What purpose does epigenetic regulation serve?

Samson T. Jacob
3 min readMay 9, 2023

--

Epigenetics is a field of biology that explores the molecular mechanisms underlying changes in gene activity and expression without alterations to the DNA sequence itself. Epigenetic modifications can be inherited from one generation to the next or arise from environmental factors, such as diet, stress, or exposure to toxins. One key function of epigenetic regulation is to enable cells to differentiate into distinct cell types with specialized functions while maintaining a stable genome across multiple generations.

The central dogma of molecular biology states that DNA is transcribed into RNA, then translated into proteins. However, not all genes are active at all times in all cells. For example, liver cells must produce enzymes that detoxify harmful compounds, whereas nerve cells must transmit electrical signals along their axons. These differences in gene expression are due to epigenetic modifications, which influence how tightly DNA is packaged around histone proteins, and whether or not certain regions of DNA are accessible to the transcription machinery.

DNA methylation is one of the most well-studied epigenetic modifications, which involves adding a methyl group (-CH3) to cytosine nucleotides within a CpG dinucleotide context. CpG islands are regions of the genome rich in CpG dinucleotides, which tend to be near gene promoters. Methylation of these CpG islands can silence gene expression by recruiting repressive chromatin-modifying complexes that prevent access of transcription factors to the promoter region. Conversely, the demethylation of CpG islands can activate gene expression by making the promoter more accessible to the transcription machinery.

Another important epigenetic modification is histone acetylation, which involves adding an acetyl group (-COCH3) to lysine residues on histone tails. Acetylation neutralizes the positive charge on histones, thereby reducing their affinity for negatively charged DNA. This leads to a more relaxed chromatin structure that allows greater transcription machinery access to the underlying DNA sequence. Conversely, histone deacetylase (HDACs) deacetylation causes chromatin compaction and gene silencing.

Epigenetic modifications can also occur via non-coding RNAs, which are transcribed from DNA but do not encode proteins. For example, microRNAs (miRNAs) are short RNA molecules that bind to complementary sequences on target mRNAs and destabilize or degrade them. By regulating mRNAs’ stability and translational efficiency, miRNAs can indirectly affect gene expression and cellular phenotype. Other non-coding RNAs, such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), have also been implicated in epigenetic regulation, although their precise functions are still being elucidated.

During embryonic development, different cell types must arise from a single totipotent zygote, which has the potential to give rise to all cell types in the body. Epigenetic modifications play a critical role in this process by marking certain regions of the genome for activation or repression in a lineage-specific manner. For example, genes coding for muscle-specific proteins are silenced in liver cells by DNA methylation. In contrast, they are activated in muscle cells by demethylation and recruitment of activating chromatin-modifying complexes.

In addition to development, epigenetic regulation plays a key role in aging and disease. Epigenetic changes accumulate over time, leading to gene expression and cellular function alterations that contribute to the aging process. For example, studies have shown that global DNA methylation levels decrease with age, while specific CpG sites become hypermethylated or hypomethylated. These changes can affect gene expression in DNA repair, inflammation, and metabolism. They may contribute to developing age-related diseases such as cancer, cardiovascular disease, and Alzheimer’s disease.

Epigenetic dysregulation has also been implicated in many other diseases, including autoimmune disorders, neurodegenerative diseases, and psychiatric disorders. For example, aberrant DNA methylation patterns have been observed in patients with lupus, multiple sclerosis, and schizophrenia, suggesting that epigenetic changes may contribute to the pathogenesis of these diseases. Similarly, alterations in histone acetylation have been linked to Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS).

Given the important role of epigenetic regulation in development and disease, there is great interest in developing epigenetic therapies for a wide range of conditions. One approach involves using small molecules that can modulate the activity of histone-modifying enzymes or DNA methyltransferases. For example, inhibitors of HDACs have been shown to induce differentiation and apoptosis in cancer cells while demethylating agents such as azacitidine.

--

--

Samson T. Jacob

It shows how Samson T. Jacob has led, taught, and guided people over the years. Samson T. Jacob has won a lot of awards and honors throughout his career.