The mechanism by which mammalian circadian clocks are entrained to lig
ht-dark cycles is unknown. The clock that drives behavioral rhythms is
located in the suprachiasmatic nucleus (SCN) of the brain, and entrai
nment is thought to require induction of genes in the SCN by light. A
complementary DNA subtraction method based on genomic representational
difference analysis was developed to identify such genes without maki
ng assumptions about their nature. Four clones corresponded to genes i
nduced specifically in the SCN by light, all of which showed gating of
induction by the circadian clock. Among these genes are c-fos and nur
77, two of the five early-response genes known to be induced in the SC
N by light, and egr-3, a zinc finger transcription factor not previous
ly identified in the SCN. In contrast to known examples, egr-3 inducti
on by light is restricted to the ventral SCN, a structure implicated i
n entrainment.