18 THE SCIENTIST | the-scientist.com
NOTEBOOKelements act generally as gene promoters
and that the methylation marks on these
elements could be passed from one gener-
ation to the next. Researchers have postu-
lated that transposable elements may have
methylation marks resistant to reprogram-
ming—so, in theory, these marks should be
most likely to be inherited.
In a series of experiments examining
the T cells and B cells of multiple gen-
erations of Agouti Viable Yellow mice,
the researchers screened the animals’
genomes searching for transposable ele-
ments that were methylated similarly to
the one that sits next to the Agouti gene.
The screen identified dozens of these
transposable elements but revealed that
only rarely do they work as promoters to
control the expression of adjacent genes.
The methylation marks on these trans-
posable elements are also wiped clean
and reprogrammed after fertilization, the
team found, meaning they can’t be directly
passed from generation to generation
(Cell, 175:1259–71.e13, 2018). “It’s hard to
imagine how a memory of methylation can
be transmitted from one generation to the
next if it’s being erased and reestablished
in each generation,” Ferguson-Smith says.
“This study is an enormous technical
tour de force,” Dirk Schübeler, a molec-
ular geneticist at the Friedrich Miescher
Institute for Biomedical Research in
Basel, Switzerland who was not involved
in the study, tells The Scientist. In the past,
researchers suggested that the epigeneti-
cally regulated Agouti trait was the tip of
the iceberg for DNA methylation–based
epigenetic inheritance, he says. “This
study shows there is no iceberg.”
The screen did identify one transpos-
able element that, like the element abut-
ting the Agouti gene, displayed a bit of
memory, Ferguson-Smith says, “but our
data suggested that memory is not being
conferred by DNA methylation.”
The researchers could see that methyl-
ation marks on this transposable element
were erased between generations, and
reestablished again in a form reminiscent
of what was found in the parental genera-
tion. “So we asked, what might it be that
causes that methylation to be reconstructedafter erasure in the same way [in the next
generation]?” Ferguson-Smith explains.
“We think that it’s conferred by genetics.”
The study results, she says, suggest that aparticular sequence in the genome causes
a specific methylation mark on a transpos-
able element to reconstruct itself in the off-
spring in the exact same way it existed in
the parent, and that such genetic sequences
are adjacent to the transposable elements
in the genome. So “non-genetic inheritance
could, in fact, be genetic in origin,” she says.
Schübeler says the idea is perfectly
possible, but more work needs to be done
to understand exactly how the genetic
mechanism underlying these epigenetic
marks might work.
University of California, Santa Cruz
geneticist Susan Strome, who was also
not involved in the study, notes that
even if the DNA methylation mode
of non-genetic inheritance is rare, asFerguson-Smith’s team suggests, it
doesn’t mean all other modes of non-
genetic inheritance are also rare. Modi-
fications to histone tails, which Strome’s
lab studies in worms, and small RNAs
are passed down between generations
and have epigenetic effects in at least
some organisms, she says. “I would not
extrapolate from the Ferguson-Smith
paper to say that epigenetic inheritance
is nearly non-existent.”
—Ashley YeagerHigh Time
Even a seasoned mystery novelist might
find it difficult to come up with a more
tantalizing string of clues than those left
by the Denisovans. Paleontologists found
the only remains of the ancient hominin
species in a Siberian cave in 2008. Ye t
a genetic analysis published early last
year reported that, among modern-day
human populations studied, the largest
proportion of Denisovan-derived genes,
about 5 percent, is found a watery hemi-
sphere away—in residents of Oceania, in
the South Pacific (Cell, 175:P53–61.E9).
Another study found that a distinctive
variant of the gene EPAS1 that helps Tibet-Epigenetic marks are
erased completely, and
reprogrammed twice during
the lifetime of an individual.DIG AT DEVU: Excavations on the Tibetan
Plateau have revealed thousands of
fragments of Paleolithic tools.YINGSHUAI JIN