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2015 ; 112
(14
): 4357-62
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The frequency natural antisense transcript first promotes, then represses,
frequency gene expression via facultative heterochromatin
#MMPMID25831497
Li N
; Joska TM
; Ruesch CE
; Coster SJ
; Belden WJ
Proc Natl Acad Sci U S A
2015[Apr]; 112
(14
): 4357-62
PMID25831497
show ga
The circadian clock is controlled by a network of interconnected feedback loops
that require histone modifications and chromatin remodeling. Long noncoding
natural antisense transcripts (NATs) originate from Period in mammals and
frequency (frq) in Neurospora. To understand the role of NATs in the clock, we
put the frq antisense transcript qrf (frq spelled backwards) under the control of
an inducible promoter. Replacing the endogenous qrf promoter altered
heterochromatin formation and DNA methylation at frq. In addition, constitutive,
low-level induction of qrf caused a dramatic effect on the endogenous rhythm and
elevated circadian output. Surprisingly, even though qrf is needed for
heterochromatic silencing, induction of qrf initially promoted frq gene
expression by creating a more permissible local chromatin environment. The
observation that antisense expression can initially promote sense gene expression
before silencing via heterochromatin formation at convergent loci is also found
when a NAT to hygromycin resistance gene is driven off the endogenous vivid (vvd)
promoter in the ?vvd strain. Facultative heterochromatin silencing at frq
functions in a parallel pathway to previously characterized VVD-dependent
silencing and is needed to establish the appropriate circadian phase. Thus,
repression via dicer-independent siRNA-mediated facultative heterochromatin is
largely independent of, and occurs alongside, other feedback processes.