AsianScientist (Sep. 30, 2015) – Researchers have uncovered the epigenetic mechanisms stem cells use to inhibit virus expression. This work, published in Cell, provides new molecular targets which could advance stem cell therapeutics and diagnostics.
Several stem cell types including embryonic and hematopoietic stem cells are known to be capable of suppressing the activities of infected viruses and viral DNA residing in the host genome. This characteristic property, known as proviral silencing has not been fully understood.
In the present study, a team of scientists led by Dr. Jonathon Loh at Institute of Molecular and Cell Biology, a research institute under Singapore’s Agency for Science, Technology and Research (A*STAR), designed a novel assay which allowed them to screen all the genes present in embryonic stem cells.
Through the screening platform, the team identified 303 genes and 148 biological processes and pathways linked to proviral silencing, suggesting that proviral silencing is controlled by coordinated mechanisms involving multiple cellular pathways. Some classes of molecules identified were histone chaperons, sumoylation factors and chromatin modifiers. In particular, the scientists found that two genes, Chaf1a and Sumo2, are the key factors linked to proviral silencing.
They found that Chaf1a and Sumo2 are directly recruited to endogenous retroviruses, where they repress gene transcription with other complexes. This epigenetic silencing of gene expression inhibits normal infection by these viruses in stem cells.
Further studies on the roles of Chaf1a and Sumo2 in stem cell proviral silencing can shed new light on stem cells and virus biology that could translate into valuable therapeutic and diagnostic applications.
“This is the first detailed study on proviral silencing in embryonic stem cells, and it helped us gain a deeper understanding of stem cells and its unique proviral silencing ability.”
“With the new insights, we can better identify the good stem cells and use them more efficiently and safely in clinical therapies. We can also devise diagnostic approaches by studying the activities of the virus DNA within stem cells in various diseased conditions,” said Loh.
The article can be found at: Yang et al. (2015) Systematic Identification of Factors for Provirus Silencing in Embryonic Stem Cells.
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Source: Agency for Science, Technology and Research.
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