Gearing-up for spring – Rapid activation of specific genes readies the mammalian body for seasonal change

The genes that regulate the process called photoperiodism—the seasonal responses induced
in organisms by changing day length—have been found by researchers from the RIKEN Center
for Developmental Biology, Kobe, and Kinki University, Osaka. Led by Koh-hei Masumoto
and Hiroki R. Ueda from RIKEN, the researchers also discovered how these genes can be
activated within a single day1. The work bears relevance to seasonal human disorders,
such as winter depression, and symptoms associated with conditions such as bipolar
Organisms need to alter body functions and behavior to accommodate seasonal changes
in their environment. The measurement of day length is one obvious way of
determining the time of year. To this end, the body uses its internal circadian clock, and
against this background measures the extent and timing of light and dark.
The team noted that an increase in day length induces activity in the gene for thyroid
stimulating hormone beta (TSHβ) in the pars tuberalis (PT) region of the pituitary gland.
TSHβ plays a key role in the pathway that regulates photoperiodism in vertebrate animals.
However, the detailed mechanism that links information about day length with induction
of the production of TSHβ is unknown.
Masumoto, Ueda and colleagues found the genes that stimulate the activity of the TSHβ
gene in mammals by observing the activity of genes in the PT of photoperiod-responsive
mice under chronic ’short-day’ (eight hours of light) and ‘long-day’ (16 hours) conditions.
They identified 57 genes stimulated by short days and 246, including TSHβ, by long days.
Then, the researchers placed chronic short-day mice into a long-day regime—they switched
off the lights eight hours later—and observed that it took five days for TSHβ to become
fully active. They could, however, stimulate full activity of TSHβ within a single 24-hour
period if they subjected the mice to a short burst of light during a sensitive ‘photo-inducible’
period late at night. Thirty-four other long-day genes responded in the same way, including the
transcription factor, Eya3, which seemed a likely candidate for regulating TSHβ activity. In
laboratory studies, the researchers determined that Eya3 and its partner binding factor Six1
do indeed act together to activate TSHβ. And this activity is enhanced by two other genes,
Tef and Hlf.
“We are next planning to identify the upstream gene of Eya3,” Ueda says. “And we are also hoping
to elucidate why the photo-inducible phase is late at night.”