Epigenetics Are Different Than Mutations in That Mutations

DNA methylation
is a chemic process that adds a methyl group to DNA. It is highly specific and e’er happens in a region in which a
cytosine
nucleotide
is located next to a
guanine
nucleotide that is linked past a phosphate; this is called a CpG site (Egger
et al., 2004; Jones & Baylin, 2002; Robertson, 2002). CpG sites are methylated by one of three enzymes called Deoxyribonucleic acid methyltransferases (DNMTs) (Egger
et al., 2004; Robertson, 2002). Inserting methyl groups changes the appearance and structure of DNA, modifying a
gene‘s interactions with the machinery within a
jail cell‘south
nucleus
that is needed for
transcription. DNA methylation is used in some genes to differentiate which gene copy is inherited from the father and which cistron copy is inherited from the mother, a phenomenon known as
imprinting.

Histones
are proteins that are the principal components of
chromatin, which is the complex of Deoxyribonucleic acid and proteins that makes up chromosomes. Histones act as a spool effectually which Deoxyribonucleic acid can wind. When histones are modified subsequently they are translated into poly peptide (i.due east., post-translation modification), they can influence how chromatin is arranged, which, in plow, can determine whether the associated chromosomal DNA will be transcribed. If chromatin is non in a compact form, information technology is active, and the associated Deoxyribonucleic acid tin exist transcribed. Conversely, if chromatin is condensed (creating a complex called
heterochromatin), then it is inactive, and DNA transcription does not occur.

There are two main means histones tin can be modified:
acetylation
and methylation. These are chemical processes that add either an acetyl or methyl grouping, respectively, to the amino acid lysine that is located in the histone. Acetylation is normally associated with active chromatin, while deacetylation is mostly associated with heterochromatin. On the other hand, histone methylation can be a
marker
for both active and inactive regions of chromatin. For instance, methylation of a particular lysine (K9) on a specific histone (H3) that marks silent DNA is widely distributed throughout heterochromatin. This is the type of epigenetic change that is responsible for the inactivated
X chromosome
of females. In contrast, methylation of a different lysine (K4) on the aforementioned histone (H3) is a marker for active genes (Egger
et al., 2004).

Genes can too be turned off by
RNA
when it is in the class of antisense transcripts, noncoding RNAs, or RNA
interference. RNA might touch on
gene expression
past causing heterochromatin to form, or by triggering histone modifications and Deoxyribonucleic acid methylation (Egger
et al., 2004).

The first man disease to be linked to epigenetics was cancer, in 1983. Researchers establish that diseased tissue from patients with colorectal cancer had less Dna methylation than normal tissue from the same patients (Feinberg & Vogelstein, 1983). Because methylated genes are typically turned off, loss of DNA methylation tin can cause abnormally loftier gene activation by altering the organisation of chromatin. On the other hand, likewise much methylation can disengage the piece of work of protective
tumor suppressor
genes.

As previously mentioned, Dna methylation occurs at CpG sites, and a majority of CpG cytosines are methylated in mammals. All the same, there are stretches of Deoxyribonucleic acid almost
promoter
regions that have higher concentrations of CpG sites (known equally CpG islands) that are free of methylation in normal cells. These CpG islands go excessively methylated in cancer cells, thereby causing genes that should non be silenced to plough off. This abnormality is the trademark epigenetic alter that occurs in tumors and happens early in the evolution of cancer (Egger
et al., 2004; Robertson, 2002; Jones & Baylin, 2002). Hypermethylation of CpG islands can cause tumors by shutting off tumor-suppressor genes. In fact, these types of changes may be more than common in human cancer than DNA sequence mutations (Effigy two).

Furthermore, although epigenetic changes exercise not modify the sequence of DNA, they can cause mutations. About half of the genes that crusade familial or inherited forms of cancer are turned off past methylation. Well-nigh of these genes usually suppress tumor formation and assist repair DNA, including O⁶-methylguanine-Dna methyltransferase (MGMT), MLH1
cyclin-dependent kinase
inhibitor 2B (CDKN2B), and
RASSF1A. For example, hypermethylation of the promoter of
MGMT
causes the number of G-to-A mutations to increase (Figure 2).

Hypermethylation can too lead to instability of microsatellites, which are repeated sequences of DNA. Microsatellites are common in normal individuals, and they ordinarily consist of repeats of the dinucleotide CA. Besides much methylation of the promoter of the
DNA repair
factor
MLH1
can make a
microsatellite
unstable and lengthen or shorten it (Figure 2). Microsatellite instability has been linked to many cancers, including colorectal, endometrial, ovarian, and gastric cancers (Jones & Baylin, 2002).

Fragile X
syndrome
is the most frequently inherited mental inability, especially in males. Both sexes can be affected by this condition, but considering males merely have one Ten
chromosome, i fragile Ten will bear upon them more than severely. Indeed, fragile 10 syndrome occurs in approximately one in 4,000 males and 1 in 8,000 females. People with this syndrome have severe intellectual disabilities, delayed verbal development, and “autistic-like” beliefs (Penagarikano
et al., 2007).

Fragile X syndrome gets its name from the way the role of the X chromosome that contains the gene aberration looks under a microscope; information technology ordinarily appears equally if it is hanging by a thread and easily brittle (Figure 3). The syndrome is caused by an aberration in the
FMR1
(fragile X mental retardation 1) gene. People who do not have frail 10 syndrome have vi to 50 repeats of the trinucleotide CGG in their
FMR1
gene. Still, individuals with over 200 repeats take a total
mutation, and they unremarkably show symptoms of the syndrome. Besides many CGGs cause the CpG islands at the promoter region of the
FMR1
gene to go methylated; normally, they are not. This methylation turns the gene off, stopping the
FMR1
cistron from producing an important
protein
chosen frail Ten mental retardation poly peptide. Loss of this specific protein causes fragile X syndrome. Although a lot of attention has been given to the CGG expansion mutation as the cause of fragile 10, the epigenetic change associated with
FMR1
methylation is the real syndrome culprit.

Fragile 10 syndrome is not the only disorder associated with mental retardation that involves epigenetic changes. Other such conditions include Rubenstein-Taybi, Coffin-Lowry, Prader-Willi, Angelman, Beckwith-Wiedemann, ATR-X, and Rett syndromes (Table i).