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2014 ; 24
(12
): 1341-1346
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Zelda potentiates morphogen activity by increasing chromatin accessibility
#MMPMID24909324
Foo SM
; Sun Y
; Lim B
; Ziukaite R
; O'Brien K
; Nien CY
; Kirov N
; Shvartsman SY
; Rushlow CA
Curr Biol
2014[Jun]; 24
(12
): 1341-1346
PMID24909324
show ga
Zygotic genome activation (ZGA) is a major genome programming event whereby the
cells of the embryo begin to adopt specified fates. Experiments in Drosophila and
zebrafish have revealed that ZGA depends on transcription factors that provide
large-scale control of gene expression by direct and specific binding to gene
regulatory sequences. Zelda (Zld) plays such a role in the Drosophila embryo,
where it has been shown to control the action of patterning signals; however, the
mechanisms underlying this effect remain largely unclear. A recent model proposed
that Zld binding sites act as quantitative regulators of the spatiotemporal
expression of genes activated by Dorsal (Dl), the morphogen that patterns the
dorsoventral axis. Here we tested this model experimentally, using enhancers of
brinker (brk) and short gastrulation (sog), both of which are directly activated
by Dl, but at different concentration thresholds. In agreement with the model, we
show that there is a clear positive correlation between the number of Zld binding
sites and the spatial domain of enhancer activity. Likewise, the timing of
expression could be advanced or delayed. We present evidence that Zld facilitates
binding of Dl to regulatory DNA, and that this is associated with increased
chromatin accessibility. Importantly, the change in chromatin accessibility is
strongly correlated with the change in Zld binding, but not Dl. We propose that
the ability of genome activators to facilitate readout of transcriptional input
is key to widespread transcriptional induction during ZGA.
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