A memorable inheritance

Scientists discover some gene silencing is not based on cues from DNA sequences, but from molecular memory thanks to chemical tags

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BLOOMINGTON, Ind.— Epigenetics has become an area of growing interest as research uncovers the extent to which it plays a role in health and diseases. It’s of particular interest for many as diseases such as cancer have been recognized as having an epigenetic base. And some of the latest epigenetic research has come from a team of scientists at Indiana University, who have discovered how acquired traits are passed between generations via epigenetic inheritance. The discovery was made by a team of 12 scientists from Indiana University, led by biologist and biochemist Craig Pikaard.
The team tested and identified the relationship between histone deacetylase 6, an enzyme that removes acetyl groups from histones, and the CG DNA sequence maintenance methyltransferase, MET1, and found that their relationship can help explain the continuation of epigenetic memory that leads to silent locus identity, a pre-established state required for a cell to provide the loci with the machinery that actually silences genes in a process known as RNA-directed DNA methylation. The process involves short-interfering RNAs (siRNA), small RNA molecules that guide the addition of methyl groups to matching DNA strands, which renders genes inactive.
“Importantly, this work shows that silent locus identity is required for, but separable from, actual gene silencing,” Pikaard said in a press release. “We’ve found that epigenetic inheritance is a two-step process, with the heritable specification of silent locus identity occurring before actual silencing of the locus can occur.”
The research has illuminated the fact that cells are not aware of which genes to silence based on genetic information written into DNA sequences, but because of heritable chemical markers added to the genes. The plant cells know to silence a genetic locus in successive generations based on chemical marks found on the chromatin; by adding or removing one-carbon (methyl) or two-carbon (acetyl) chemical tags, chromatin can be modified to provide additional, epigenetic information to a locus besides what is encoded in the DNA. This ability is a kind of epigenetic memory that provides silent locus identity, according to Pikaard,
“Collectively, our results show that silent locus identity is perpetuated from generation to generation through the actions of HDA6 and MET1,” Pikaard added. “These activities are not sufficient to silence the loci but maintain a chromatin state that is required for Pol IV recruitment, siRNA biogenesis and RdDM, which is what ultimately silences the loci.”
When the team removed the RdDM pathway in Pol IV and Pol V mutant strains of the model plant Arabidopsis thaliana (rockcress), all gene silencing was lost, but silent locus identity remained. They then removed the HDA6 and MET1-dependent process that specifies silent locus identity and, importantly, the epigenetic memory required for silent locus identity was lost and unable to be regained.
The research, “A two-step process for epigenetic inheritance in Arabidopsis,” was published on March 20 in Molecular Cell.
Scientists discover some gene silencing is not based on cues from DNA sequences, but from molecular memory thanks to chemical tags

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