DNA methyltransferases (DNMTs) catalyse
the methylation of cytosine by moving a methyl group from
S-adenosyl-L-methionine (SAM) to the fifth carbon atom of cytosine.
There are different types of DNMTS: DNMT1,
DNMT2, DNMT3a and DNMT3b.
DNMT1: the major maintenance
methyltransferase that copies DNA methylation patterns to daughter strands
during DNA replication)
DNMT2: it is a DNA methyltransferase
homolog, with the 10 sequence motifs common to every DNA methyltransferases.
DNMT3a and DNMT3b: they are the de novo
methyltransferases that set up the methylation patterns in the early stages of
After cytosine is methylated,
5-methylcytosine is formed, while methylation occurs at 5 identical locations
on the pyrimidine ring where the methyl group of thymine is located.
5-methylcytosine is then deanimated and converted back into thymine, leading to
a T:G mismatch. Repair mechanisms either alter it back into a C:G pair, or they
could substitute g for A, creating an A:T pair, which changes the bases and
causes a mutation. Cancer may be caused when tumour suppressor genes are
silenced by DNA methylation during carcinogenesis.
The function of histones is to package and
order DNA, while DNA molecules are wrapped around 8 histones. The main ways to
modify histones is by the addition of an acetyl, methyl or phosphate group, or
other processes such as ubiquitylation and sumoylation. The modifications make
the gene either more or less accessible to transcription factors, which means
that these changes either activate or deactivate the gene. Histone
modifications are covalent post-translational modifications (PTM). They can
affect gene expression by altering the structure of chromatin.
Histone acetylation occurs when histone
acetyltransferases (HATs) catalyse the addition of an acetyl group from acetyl
coenzyme A. the process may be increased by the inhibition of histone
The transfer of methyl groups by histone
methyltransferases (HMTs) to histones. The methyl groups are added to histone
Histones are present as DNA-wrapped
protein octamers, which are made up of four identical core histones (H2A, H2B,
H3 AND H4). When histone methylation or demethylation occurs, the structure may
become loosened or restricted, leading to transcriptional repression or
this mainly affects serine, threonine and
tyrosine residues. A Phosphoryl group is added to up to four nucleosomal
histone tails (they are involved in chromatin remodelling). A function of
histone phosphorylation is to respond to DNA damage.