DNA methyltransferases (DNMTs) catalysethe methylation of cytosine by moving a methyl group fromS-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 maintenancemethyltransferase that copies DNA methylation patterns to daughter strandsduring DNA replication)DNMT2: it is a DNA methyltransferasehomolog, with the 10 sequence motifs common to every DNA methyltransferases.DNMT3a and DNMT3b: they are the de novomethyltransferases that set up the methylation patterns in the early stages ofdevelopment. After cytosine is methylated,5-methylcytosine is formed, while methylation occurs at 5 identical locationson the pyrimidine ring where the methyl group of thymine is located.
5-methylcytosine is then deanimated and converted back into thymine, leading toa T:G mismatch. Repair mechanisms either alter it back into a C:G pair, or theycould substitute g for A, creating an A:T pair, which changes the bases andcauses a mutation. Cancer may be caused when tumour suppressor genes aresilenced by DNA methylation during carcinogenesis. (b) The function of histones is to package andorder DNA, while DNA molecules are wrapped around 8 histones. The main ways tomodify histones is by the addition of an acetyl, methyl or phosphate group, orother processes such as ubiquitylation and sumoylation. The modifications makethe gene either more or less accessible to transcription factors, which meansthat these changes either activate or deactivate the gene.
Histonemodifications are covalent post-translational modifications (PTM). They canaffect gene expression by altering the structure of chromatin. Histone acetylation:Histone acetylation occurs when histoneacetyltransferases (HATs) catalyse the addition of an acetyl group from acetylcoenzyme A.
the process may be increased by the inhibition of histonedeacetylases (HDACs). Histone methylation: The transfer of methyl groups by histonemethyltransferases (HMTs) to histones. The methyl groups are added to histonetails.
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Histones are present as DNA-wrappedprotein octamers, which are made up of four identical core histones (H2A, H2B,H3 AND H4). When histone methylation or demethylation occurs, the structure maybecome loosened or restricted, leading to transcriptional repression oractivation. Histone phosphorylation: this mainly affects serine, threonine andtyrosine residues. A Phosphoryl group is added to up to four nucleosomalhistone tails (they are involved in chromatin remodelling).
A function ofhistone phosphorylation is to respond to DNA damage.
