Epigenome Editing and Engineering Quiz

Epigenome Editing and Epigenetics

• Epigenetic editing is a type of genetic engineering that modifies the epigenome at specific sites using engineered molecules targeted to those sites.
• Epigenetic editing involves modifying and presenting DNA sequences to proteins and other DNA binding factors that influence DNA function.
• Epigenetics alters the expression of genes without alterations in the DNA sequence, and these alterations are stable enough to be transmitted through mitosis and sometimes meiosis.
• Epigenetic changes can also be influenced by environmental factors.

DNA Methylation

• DNA methylation is the addition of methyl groups to nucleotide bases, specifically cytosine, to produce 5-methylcytosine.
• Methylation often occurs on cytosine nucleotides immediately adjacent to guanine nucleotides, referred to as CpG dinucleotides.
• CpG islands are regions with many CpG dinucleotides and are often located in or near gene promoters.
• Methylation of CpG islands near a gene leads to repression of transcription.

Maintenance of Methylation

• Methylation of CpG dinucleotides means that two methylated cytosine bases sit diagonally across from each other on opposite strands.
• Before replication, cytosine bases on both strands are methylated, and immediately after replication, the cytosine base on the template strand is methylated, but the cytosine base on the newly replicated strand is unmethylated.
• Special methyl-transferase enzymes recognize the hemi-methylated state of CpG dinucleotides and add methyl groups to the unmethylated cytosine bases, resulting in two new DNA molecules that are fully methylated.

Repression of Transcription by DNA Methylation

• The methyl group of 5-methylcytosine sits within the major groove of the DNA molecule, inhibiting the binding of transcription factors and other proteins required for transcription.
• The presence of the methyl group in the major groove attracts certain proteins that directly repress transcription.
• DNA methylation also attracts histone deacetylase enzymes, which remove acetyl groups from the tails of histone proteins, altering chromatin structure in a way that represses transcription.

Histone Modifications

• Histone modifications can also occur through the addition of phosphates, methyl groups, acetyl groups, and ubiquitin.
• These modifications can occur at different amino acids on different histones and create more than 100 unique potential changes in the histones.
• Many of these modifications alter chromatin structure and affect transcription of genes.

Specific Histone Modifications

• Histone acetylation: addition of acetyl groups to amino acids in the histone tails, generally destabilizing chromatin structure and increasing transcription.
• Histone methylation: addition of methyl groups to histones, altering chromatin structure and affecting transcription, with different effects depending on the specific amino acid methylated.
• Histone ubiquitination: modification of histones, influencing other molecular processes such as DNA repair and cell cycle checkpoint signaling.

Importance of Epigenome Editing

• Epigenetic effects have been linked to oncogenesis, progression, and treatment of cancer.
• Epigenetics plays a role in many cellular processes, making epigenome editing a crucial area of research.