An epigenetic change, a form of DNA control, that deactivates some genes linked to cancer late in human development has been conserved for more than 400 million years, new research suggests.
Researchers uncovered that genes turned on in some cancers in humans also exist in zebrafish - but are 'silenced' within just hours of fertilisation. The study sheds new light on how our epigenetics can regulate genes, some of which are linked to cancer development later in life, over large evolutionary distances. It also uncovers significant differences between how the epigenome 'resets itself' in zebrafish and human embryos, which may guide future studies on epigenetic inheritance.
"We've shown that we have conserved this embryonic event that switches off genes linked to cancers in humans," says the senior author. "It's intriguing and we still don't know why it's happening, but it suggests just how important to human health it is to keep these genes silenced." The findings are published in the journal Nature Communications.
At first glance, humans and zebrafish (a tiny species of fish native to South Asia) hardly seem related - in fact, our common evolutionary ancestor dates back more than 400 million years.
But genetically, zebrafish and humans are not so different - we share around 70% of protein-producing genes. The team set out to investigate how conserved the epigenetic changes, that control how DNA is 'read', are during the development of an embryo.
Genes are in part controlled by methylation - tags on DNA that 'block' genes from being read.
The researchers first isolated primordial germ cells, the precursor cells of sperm and egg, from developing zebrafish embryos and generated whole genome bisulfite sequencing (WGBS) data - a snapshot of all the DNA methylation in the cell.
The team uncovered fundamental differences in how DNA is methylated in mammalian and zebrafish embryos.
In humans, these DNA methylation tags are mostly 'swept clean' when a sperm fertilises an egg, and then gradually methylated again, to ensure the embryo can develop correctly. Instead, zebrafish embryos retain the methyl group pattern of the father.
In this study, the researchers found that primordial germ cells of zebrafish do not reset their methylation patterns either, but inherit paternal DNA methylation patterns. This contrasts with findings in mammalian primordial germ cells, which undergo a second 'sweep cleaning' of their DNA methylation tags. The researchers say this finding sheds light on the molecular principles of germline development and highlights zebrafish as a useful experimental model to study how epigenetic signatures are inherited throughout generations.
Further, the researchers screened how DNA is methylated in zebrafish embryos, at four stages of development. They discovered 68 genes that were methylated and turned off early during embryonic development, within 24 hours of fertilisation.
"What was interesting is that most of these genes belong to a group called cancer testis antigens," says co-first author of the study. "Our work shows that these are some of the very first genes that are 'silenced', or targeted by DNA methylation, in both zebrafish and mammals."
The genes that code for cancer testis antigens, or CTAs for short, are only active in the male testis, but are turned off in all other tissues, in humans. For an unknown reason, CTA genes are turned on again in some cancers, such as melanomas.
"Mammals and fish have very different strategies when it comes to developing an embryo," says the senior author. "But in spite of these very different strategies, it appears that the control of CTA genes are conserved throughout evolution."
While the work sheds new light on our evolution, it may have potential to impact the future of human health. Drugs which target CTAs are already being investigated as a potential therapy for cancers. The current study provides more evidence on how significant CTAs are, and how tightly controlled they have been over the course of evolution.
https://www.garvan.org.au/news-events/news/ancient-epigenetic-changes-silence-cancer-linked-genes
https://www.nature.com/articles/s41467-019-10895-6
Latest News
Complete vascularization of…
By newseditor
Posted 28 Mar
Immune cells identified as…
By newseditor
Posted 28 Mar
TB blood test which could d…
By newseditor
Posted 27 Mar
Propionate supplementation…
By newseditor
Posted 27 Mar
Role of human Kallistatin i…
By newseditor
Posted 26 Mar
Other Top Stories
Long-non coding RNAs promote breast cancer metastasis
Read more
How shattered chromosomes (chromothripsis) make cancer cells drug-r…
Read more
Phase 3 clinical trial reveals life saving drug for acute myeloid l…
Read more
Brain cancer linked to tissue healing
Read more
The hexosamine biosynthesis pathway is a targetable liability in KR…
Read more
Protocols
Spatial proteomics in neuro…
By newseditor
Posted 28 Mar
All-optical presynaptic pla…
By newseditor
Posted 23 Mar
Epigenomic tomography for p…
By newseditor
Posted 20 Mar
A mouse DRG genetic toolkit…
By newseditor
Posted 17 Mar
An optogenetic method for t…
By newseditor
Posted 13 Mar
Publications
A microfluidic platform int…
By newseditor
Posted 28 Mar
Salmonella manipulates macr…
By newseditor
Posted 28 Mar
BHLHE40/41 regulate microgl…
By newseditor
Posted 28 Mar
Balancing neuronal activity…
By newseditor
Posted 28 Mar
OSBP-mediated PI(4)P-choles…
By newseditor
Posted 28 Mar
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar