lecture 20

What is DNA methylation?

An epigenetic process where cells add a methyl group to nucleotides, helping regulate gene expression, repress transcription (by recruiting gene-silencing proteins or blocking transcription factor binding), and changing during development and in the nervous system.[cite: 1]

What is the chemical structure resulting from cytosine DNA methylation?

5-methylcytosine[cite: 1]

What are some examples of cytosine DNA methylation rates across species?

~14% in Arabidopsis thaliana, 4% to 8% in Physarum, 7.6% in Mus musculus, 2.7% in Escherichia coli, and 0.03% in Drosophila.[cite: 1]

Where else has adenine methylation been observed?

In bacterial and plant DNA, and recently also in mammalian DNA, though it has received considerably less attention.[cite: 1]

What are DNA Methyltransferases (DNMTs)?

Enzymes that play a crucial role in adding methyl groups to DNA (primarily affecting cytosine bases), vital for regulating gene expression and maintaining genomic stability.[cite: 1]

What is the function and characteristic of DNMT1?

Maintenance DNMT; most abundant in mammals, copies methylation patterns during DNA replication.[cite: 1]

What is the function and characteristic of DNMT3A?

De novo methylation; establishes new methylation patterns, particularly during early development.[cite: 1]

What is the function and characteristic of DNMT3B?

De novo methylation; similar to DNMT3A, involved in gene regulation and development.[cite: 1]

What is the function and characteristic of DNMT2?

RNA methylation; primarily methylates tRNA, not DNA; renamed TRDMT1 to reflect its function.[cite: 1]

How does DNA methylation context differ between plants and mammals?

In plants, DNA methylation is found in CG, CNG, or CNN contexts. In mammals, DNA methylation is almost exclusively found in CpG dinucleotides with cytosines on both strands usually methylated.[cite: 2]

Where can non-CpG methylation be observed?

In embryonic stem cells and has also been indicated in neural development.[cite: 2]

What is the typical mammalian DNA methylation landscape in somatic cells?

~75% of CpG dinucleotides are methylated in somatic cells, and DNA methylation acts as a default state that must be specifically excluded from defined locations (such as unmethylated CpG islands).[cite: 2]

How many CpG islands are in the human genome and what are their characteristics?

Excluding repeated sequences, there are around 25,000 CpG islands (75% of which are less than 850 bp long). ~50% are located in gene promoter regions, and 25% lie in gene bodies often serving as alternative promoters.[cite: 2]

What percentage of human genes have a CpG island in their promoter region?

Around 60% to 70% of human genes.[cite: 2]

What is genomic imprinting?

An epigenetic phenomenon where a DNA segment is marked (imprinted) during egg or sperm formation, resulting in monoallelic gene expression depending on parental origin throughout the life of the individual.[cite: 2]

Where do N-terminal histone tails contact DNA?

In the phosphodiester backbone and minor grooves.[cite: 3]

Which amino acids are N-terminal histone tails particularly rich in?

Glycine (G), Lysine (K), Arginine (R), Serine (S), and Threonine (T).[cite: 4]

What is the mechanism of histone methylation?

The addition of methyl groups to lysine (K) or arginine (R) residues on the N-terminal tails of histones H3 and H4, catalyzed by histone methyltransferases (HMTs) using S-adenosyl-L-methionine as the methyl donor.[cite: 3]

What are the possible methylation states for lysine and arginine residues?

Lysine can be mono-, di-, or tri-methylated, while arginine can be mono- or di-methylated (either symmetrically or asymmetrically).[cite: 3]

What is the functional effect of histone methylation?

It does not change the positive charge of the histone, but creates specific binding sites for "reader" proteins that influence chromatin state and gene expression.[cite: 3]

What are protein Post-translational modifications (PTMs)?

Phosphorylation of S, T, and Y residues; acetylation, methylation, SUMOylation, and ubiquitination of K residues; and methylation of R residues.[cite: 4, 5]

What is arginine methylation and what enzymes catalyze it?

The addition of methyl groups to arginine residues by protein arginine methyltransferases (PRMTs), which affects protein function, RNA-binding protein stability, signal transduction, and transcriptional regulation.[cite: 4]

What are histone acetylation and deacetylation?

Processes by which lysine (K) residues within the N-terminal tail protruding from the histone core are acetylated and deacetylated as part of gene regulation, controlling how dense or relaxed DNA is.[cite: 4, 5]

Which enzymes catalyze histone acetylation and deacetylation?

Acetylation is catalyzed by Histone Acetyltransferases (HATs); deacetylation is catalyzed by Histone Deacetylases (HDACs I, II, IV, and HDAC III / SIRTs).[cite: 5]

What is epigenetics?

The study of heritable phenotype changes that do not involve changes in the underlying