DNA METHYLATION & EPIGENETIC REGULATION: CPG ISLANDS, DNMTS, TET ENZYMES & METHYLATION PATTERNS ๐ŸŽ—

“DNA methylation is an epigenetic mark” involved in regulating transcription and maintaining cellular identity. -Dr. Peter A. Jones

๐Ÿงฌ DNA methylation is an epigenetic mechanism regulating gene activity without changing the DNA sequence. Most commonly, a methyl group is added to the 5-carbon of cytosine within 5′-CpG-3′ dinucleotides, forming 5-methylcytosine (5mC). It contributes to transcriptional regulation, cellular differentiation, genomic stability, development, genomic imprinting and cell identity.

๐Ÿ”น CpG islands are GC- and CpG-rich regions, often near gene promoters. Many promoter-associated CpG islands remain unmethylated when genes are active, whereas aberrant promoter methylation can contribute to transcriptional repression through altered regulatory-factor binding and recruitment of chromatin-remodelling proteins. Importantly, methylation is context-dependent: its effects vary across promoters, enhancers, gene bodies and repetitive elements.

๐Ÿ”น DNMTs are the principal “writers” of DNA methylation. DNMT3A and DNMT3B establish de novo methylation patterns, particularly during development and differentiation, while DNMT1 has a major role in maintaining methylation after DNA replication. Together, they help preserve epigenetic information across cell divisions.

๐Ÿ”น TET1, TET2 and TET3 enable active methylation remodeling by oxidizing 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). These derivatives can enter DNA-repair pathways to facilitate demethylation. Thus, the methylome reflects a dynamic balance between establishment, maintenance and removal of methylation.

➡️ During embryogenesis and differentiation, methylation landscapes undergo extensive remodeling. Genomic imprinting is a notable example of parent-of-origin-specific methylation. In cancer, global hypomethylation can coexist with locus-specific hypermethylation, contributing to genomic instability and inappropriate silencing of regulatory genes.

⚠️ In an Oystershell, DNA methylation is better understood as a context-dependent regulatory system than a simple molecular switch. CpG islands, DNMTs and TET enzymes collectively shape the methylome, linking developmental and cellular signals to gene regulation. High-resolution epigenomic mapping is expanding our understanding of development, aging, cancer and disease.

Abubakar Abubakar ✍

• Jones PA. Nat Rev Genet. 2012;13:484-492.

• Lyko F. Nat Rev Genet. 2018;19:81-92.

• Tahiliani M, et al. Science. 2009;324:930-935.

• Smith ZD, et al. Nature. 2014;511:611-615.

#DNAMethylation #Epigenetics #HumanGenetics #Genomics #DNMT #TET #CpGIslands #CancerBiology #PrecisionMedicine #Research #Bioinformatics #CRISPR #NGS #PGT #IVF #ART ⚕️

Comments

Post a Comment

Popular posts from this blog

BALANCED TRANSLOCATION

Image
"AN EXCHANGE CAN HAPPEN WITHOUT A GAIN OR LOSS, YET IT MAY PRODUCE SOME UNEXPECTED SIDE EFFECTS" ๐Ÿงฌ Balanced translocation is a type of chromosomal rearrangement where two segments of chromosomes are exchanged without any loss or gain of genetic material. This results in a rearrangement of genetic material within the chromosomes without any significant disruption. Balanced translocations typically involve the exchange of segments between non-homologous chromosomes, meaning that the segments are exchanged between different pairs of chromosomes.          ๐Ÿ”น Individuals with balanced translocations often do not display any outward physical signs or symptoms, as the total amount of genetic material remains the same. However, balanced translocations can have implications for health and reproduction. In some cases, balanced translocations can lead to infertility, recurrent miscarriages, or the potential for offspring to inherit unbalanced translocations, which do invo...
Read more

UNDERSTANDING ACMG GUIDELINES & CLINICAL CLASSIFICATION OF GENETIC VARIANTS

Image
“๐“๐“ธ ๐“ผ๐“ฒ๐“ท๐“ฐ๐“ต๐“ฎ ๐“ต๐“ช๐“ซ๐“ธ๐“ป๐“ช๐“ฝ๐“ธ๐“ป๐”‚ ๐“ฑ๐“ช๐“ผ ๐“ฎ๐“ท๐“ธ๐“พ๐“ฐ๐“ฑ ๐“ญ๐“ช๐“ฝ๐“ช; ๐“ฌ๐“ธ๐“ต๐“ต๐“ช๐“ซ๐“ธ๐“ป๐“ช๐“ฝ๐“ฒ๐“ฟ๐“ฎ ๐“ฌ๐“พ๐“ป๐“ช๐“ฝ๐“ฒ๐“ธ๐“ท ๐“ฒ๐“ผ ๐“ฝ๐“ฑ๐“ฎ ๐“ฏ๐“พ๐“ฝ๐“พ๐“ป๐“ฎ ๐“ธ๐“ฏ ๐“ฐ๐“ฎ๐“ท๐“ธ๐“ถ๐“ฒ๐“ฌ ๐“ถ๐“ฎ๐“ญ๐“ฒ๐“ฌ๐“ฒ๐“ท๐“ฎ.” - Professor Heidi Rehm ๐Ÿงฌ Genomic medicine has moved from discovery to daily clinical decision-making. At the center of this shift are the 2015 standards from the American College of Medical Genetics & Genomics (ACMG), which established a structured framework for interpreting sequence variants.    ๐Ÿ”น Genetic variants influence disease risk, diagnosis, prognosis, & therapeutic strategy. Without standardized interpretation, clinical decisions become inconsistent. The ACMG/AMP framework addresses this by integrating multiple evidence streams into five categories: 1. Pathogenic (Class 5) 2. Likely Pathogenic (Class 4) 3. Variant of Uncertain Significance [VUS] (Class 3) 4. Likely Benign (Class 2) 5. Benign (Class 1) This tiered system reduces interpretive subjectivity & improves reproducibility...
Read more

ERYTHEMA INFECTIOSUM

Image
"YOU MADE IT THROUGH PANDEMICS, BUT THERE'S STILL A FIFTH DISEASE" ๐Ÿงฌ Erythema Infectiosum, also known as Fifth Disease, is a viral infection caused by parvovirus B19. It is most common in children but can affect people of all ages. The characteristic symptom of erythema infectiosum is a distinctive rash on the cheeks giving a "slapped cheek" appearance, followed by a lacy rash on the trunk and limbs.            ๐Ÿ”ฌDiagnosis of erythema infectiosum is usually based on the characteristic rash and a history of exposure to the virus. In some cases, blood tests may be done to confirm the presence of parvovirus B19 antibodies.            ๐Ÿ’Š Treatment for erythema infectiosum is usually symptomatic, as the infection typically resolves on its own. Rest, fluids, and over-the-counter pain relievers may be recommended to alleviate symptoms.            ๐Ÿ’‰ Preventing the spread of erythema infectios...
Read more