Thursday, June 24, 2010
Some viruses insert themselves into the host's DNA during infection
in a process called retroviral integration, causing several
diseases, including AIDS and cancer, notes a Texas A&M
researcher who specializes in fetal diseases. However, stem cells
that give rise to the early embryo and yolk sac fight back,
inhibiting further infection by aggressively silencing the invading
viral DNA, says Michael Golding of the Department of Veterinary
Physiology and Pharmacology.
The work of the researcher was recently published
in Cell
Stem Cell.
Early mammalian embryos actually possess three stem cell lineages:
ES (embryonic stem), TS (trophectoderm stem), and XEN
(extraembryonic endoderm), which give rise to the fetus, placenta
and yolk sac respectively, the Texas A&M researcher explains.
Using the mouse as a model organism, Golding and his colleagues
demonstrate that the mechanisms silencing gene expression are
different between each of the three stem cell types.
"Much like a closed book cannot be read while an open book can, the
DNA encoding genes can either be tightly wound up and silent or in
a relaxed, open, active state," Golding explains. "The mechanisms
that control this gene packaging are called epigenetic as they
represent a level of regulation that is above or 'epi' to
genetics."
The study shows "retroviral silencing in XEN cells is epigenetic in
origin" and that "the three cell lineages of early mammalian embryo
have vastly different viral silencing strategies as well as
different capacities to suppress retroviral activity."
To examine the validity of a common assumption that these stem
cells use similar mechanisms to silence retroviruses, Golding
infected the mouse embryo stem cells with mouse leukemia virus
(MLV) and monitored the virus' activity.
ES cells showed a progressive decline in virus activity, while TS
cells had a constant level of virus activity. XEN cells, however,
exhibited extremely aggressive and rapid silencing of virus
activity, according to the study.
"Epigenetics is an exciting new field of research which is altering
the way we think about fetal nutrition and exposure to
environmental chemicals," Golding adds. "This discovery that all
three stem cell types of the early embryo utilize slightly
different mechanisms to control gene expression has profound
implications for how we diagnose and treat fetal
diseases."