Scientists have long recognised the genetic phenomenon known as epigenetic inheritance, the process by which acquired traits can be passed down through generations of a species.
However, until a recent study by a team from Indiana University, no one has known exactly how this happens. The twelve member team, led by biologist and biochemist Craig Pikaard, conducted the research on plant cells, with the intention to find out how the cells know to silence a genetic locus – the specific place on a chromosome where a gene is located – in successive generations.
The new work, published in the journal Molecular Cell, found that instead of cells intrinsically knowing which genes to silence due to information inbuilt in their DNA, they rely on chemical marks that are added to the genes. These chemical tags, displayed on complexes of DNA and proteins known as chromatin, act as a form of molecular memory which allows cells to recognise the tagged genes and remember to silence them in each new generation.
By the addition or removal of one or two carbon chain lengths from the chemical tags, the chromatin is modified in such a way that it allows additional epigenetic information to be imparted to the locus of the chromosome, supplying it with more information than what is encoded in its DNA.
“We have found that epigenetic inheritance is a two step process,” commented Pikaard on the findings, “with the heritable specification of silent locus identity occurring before actual silencing of the locus can occur”.
Silent locus identity is a pre-established state that is needed to deliver the required machinery to the loci, before a multistep process known as RNA-directed DNA Methylation (RdDM) silences the loci. RdDM uses small RNA molecules, 24 nucleotides long, which guide the additional methyl groups to matching DNA strands, rendering the genes inactive.
Pikaard and his research team also looked into how silent locus identity is perpetuated through generations. They tested and identified the relationship between histone deacetylase, an enzyme which removes acetyl groups (a two carbon chain) from histones, and MET1, a DNA sequence maintenance group of enzymes. It is through the methylation that occurs due to these enzymes that silent locus identity is perpetuated from generation to generation.
“These activities are not sufficient to silence the loci,” Pikaard reported, “but maintain a chromatin state that is required for Pol IV recruitment, siRNA biogenesis and RdDM, which is –what ultimately silences the loci”.
Epigenetic Inheritance is becoming an important area of research for scientists as diseases such as cancer are recognised to have an epigenetic basis. Any increased chances of the diseases occurring in a person are inherited through their genes. Discovering how to silence the genes related to such inherited diseases, or inherited increased risk, is crucial to the fight against them.
Daniel Di Francesco