Epigenetics
[1] The Greek prefix epi- (ἐπι- "over, outside of, around") in epigenetics implies features that are "on top of" or "in addition to" the traditional (DNA sequence based) genetic mechanism of inheritance.
Waddington held that cell fates were established during development in a process he called canalisation much as a marble rolls down to the point of lowest local elevation.
[18] In recent times, Waddington's notion of the epigenetic landscape has been rigorously formalized in the context of the systems dynamics state approach to the study of cell-fate.
For example, Adrian Bird defined epigenetics as "the structural adaptation of chromosomal regions so as to register, signal or perpetuate altered activity states.
"[7] This definition would be inclusive of transient modifications associated with DNA repair or cell-cycle phases as well as stable changes maintained across multiple cell generations, but exclude others such as templating of membrane architecture and prions unless they impinge on chromosome function.
"[24] In 2008, a consensus definition of the epigenetic trait, a "stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence," was made at a Cold Spring Harbor meeting.
Taken to its extreme, the "epigenetic code" could represent the total state of the cell, with the position of each molecule accounted for in an epigenomic map, a diagrammatic representation of the gene expression, DNA methylation and histone modification status of a particular genomic region.
More typically, the term is used in reference to systematic efforts to measure specific, relevant forms of epigenetic information such as the histone code or DNA methylation patterns.
One example that seems to refute this biophysical model for methylation is that tri-methylation of histone H3 at lysine 4 is strongly associated with (and required for full) transcriptional activation (see top Figure).
These genes are often turned on or off by signal transduction, although in some systems where syncytia or gap junctions are important, RNA may spread directly to other cells or nuclei by diffusion.
A smaller quantity of sperm RNA is transmitted from the father, but there is recent evidence that this epigenetic information can lead to visible changes in several generations of offspring.
[66] Numerous investigations have demonstrated the pivotal involvement of long non-coding RNAs (lncRNAs) in the regulation of gene expression and chromosomal modifications, thereby exerting significant control over cellular differentiation.
[67] In invertebrates such as social insects of honey bees, long non-coding RNAs are detected as a possible epigenetic mechanism via allele-specific genes underlying aggression via reciprocal crosses.
In PSI+ cells, the loss of the Sup35 protein (which is involved in termination of translation) causes ribosomes to have a higher rate of read-through of stop codons, an effect that results in suppression of nonsense mutations in other genes.
It could confer an adaptive advantage by giving cells the ability to switch into a PSI+ state and express dormant genetic features normally terminated by stop codon mutations.
[citation needed] As an example, when human mammary epithelial cells were treated with H2O2 for six hours, 8-OHdG increased about 3.5-fold in DNA and this caused about 80% demethylation of the 5-methylcytosines in the genome.
These techniques include chromatin immunoprecipitation (together with its large-scale variants ChIP-on-chip and ChIP-Seq), fluorescent in situ hybridization, methylation-sensitive restriction enzymes, DNA adenine methyltransferase identification (DamID) and bisulfite sequencing.
[130] When a strong memory is created, as in a rat subjected to contextual fear conditioning (CFC), one of the earliest events to occur is that more than 100 DNA double-strand breaks are formed by topoisomerase IIB in neurons of the hippocampus and the medial prefrontal cortex (mPFC).
[150][151] A review suggests neurobiological effects of physical exercise via epigenetics seem "central to building an 'epigenetic memory' to influence long-term brain function and behavior" and may even be heritable.
[166] The original researchers pointed out negative results in the paper's appendix that the criticism omitted in its calculations, and undertook to track which mice were siblings in the future.
In this organism, DNA methylation is associated with relics of a genome-defense system called RIP (repeat-induced point mutation) and silences gene expression by inhibiting transcription elongation.
This can provide a survival advantage under adverse conditions, exemplifying epigenetic regulation which enables unicellular organisms to respond rapidly to environmental stress.
DNA adenine methylation is important in bacteria virulence in organisms such as Escherichia coli, Salmonella, Vibrio, Yersinia, Haemophilus, and Brucella.
In Gammaproteobacteria, adenine methylation provides signals for DNA replication, chromosome segregation, mismatch repair, packaging of bacteriophage, transposase activity and regulation of gene expression.
[182][189] There exists a genetic switch controlling Streptococcus pneumoniae (the pneumococcus) that allows the bacterium to randomly change its characteristics into six alternative states that could pave the way to improved vaccines.
Additionally, lithium can impact autophagy of aberrant proteins, and opioid drugs via chronic use can increase the expression of genes associated with addictive phenotypes.
Members of the APOBEC/AID family of cytosine deaminases may concurrently influence genetic and epigenetic inheritance using similar molecular mechanisms, and may be a point of crosstalk between these conceptually compartmentalized processes.
[223] In addition, animal models demonstrated that UBASH3B expression is an indicator of caloric restriction that may drive programmed susceptibility to obesity and it is associated with other measures of adiposity in human peripherical blood.
[230] Colocalization analysis supports that variants for the majority of the CpG sites in SNP rs730775 cause genetic variation at the NFKBIE locus which is suggestible linked to rheumatoid arthritis through trans acting regulation of DNA methylation by NF-κB.
[223] As epigenetics is in the early stages of development as a science and is surrounded by sensationalism in the public media, David Gorski and geneticist Adam Rutherford have advised caution against the proliferation of false and pseudoscientific conclusions by new age authors making unfounded suggestions that a person's genes and health can be manipulated by mind control.
