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Dna Hydroxymethylation Of Mammals Essay

1205 words - 5 pages

Epigenetic changes refer to mechanisms which alter gene expression without altering the underlying DNA sequence. Sometimes, these changes are inherited throughout the cell’s life via cell division. Mechanisms that induce epigenetic changes include DNA methylation, histone modification, prions (which can be inherited without modifying the genome), and RNA signalling. This paper will focus on DNA hydroxymethylation in mammals.

DNA methylation is a postreplicative modification that occurs when a methyl (-CH3) group is added at position 5 of the cytosine pyrimidine ring and “establishes a silent chromatin state by collaborating with proteins that modify nucleosomes.” (Rudolf Jaenisch, 2003). It is found in cytosines of the dinucleotide sequence CpG, which when methylated within a gene in mammals can turn the gene off. This silencing of genes process can be found in cases of cancer in humans. (Wikipedia, DNA methylation in Cancer, 2012). The process of forming 5-methylcytosine (5mC), which makes up 1% of all DNA bases (Mamta Tahiliani, 2009), is catalysed by DNA methytransferase proteins (DNMTs). The three major ones are DNMT1, 3a and 3b, which each initiate and sustain their own unique DNA methylation patterns during differentiation, regardless of cell division cycles (Andrea Rottach, 2009).

The genome in mammals is the same in all mammalian cells, and different genes are expressed in different cell types. Most 5mCs are found in transposons, “which are repeated sequences that comprise >40% of the human genome and represent a potential threat to the function and stability of the genome” (Christina Dahl, 2011). A high percentage of DNA in mammals is methylated, with the unmethylated CpG’s residing in “CpG islands”. These islands are short sequence domains that continue to be unmethylated in spite of gene expression. (Rudolf Jaenisch, 2003). Since the question as to how these CpG islands are able to remain unmethylated has still not been answered, it has been the focus of attention on many recent studies in this field, and is still an ongoing, popular research topic.

It is important to comprehend the importance of DNA hydroxymethylation in mammals, and to do this, its role in development and biochemistry must further be investigated. 5-hydroxymethylcytosine (5hmC) was first detected around 30 years ago by Tahiliani et al (Christina Dahl, 2011) and is formed in an oxidation reaction when 5-methylcytosine (5mC) is catalysed by the Tet (Ten-Eleven-Translocation) family of proteins (Tet1, Tet2, Tet3). These proteins have proven to be involved with early embryogenesis, genome reprogramming and stem-cell differentiation. (Gilles Salbert, 2012)

This discovery has been as recent as 2009, and has been the pioneer of various breakthrough concepts in the understanding of it’s function. A recent experiment regarding the presence of 5hmC in mouse cerebellum and embryonic stem cells has established the theory that “5hmC may be an...

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