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Fig. 8. Models of Notch target gene regulation. (A) Notch signaling has multiple
inputs into twist; it regulates twist directly and
indirectly, through the repressor of twist genes. Both modes of
regulation require Notch to act as a transcriptional switch. In the absence of
Notch signaling, Su(H) interacts with corepressors [Su(H)rep] to
repress transcription of both twist and repressor of twist.
Upon activation of the Notch receptor, the intracellular domain of Notch
(Nicd) enters the nucleus and associates with Su(H). This
interaction displaces corepressors, de-represses Su(H) and allows Su(H) to
serve as a transcriptional activator [Su(H)act]. Hence, Notch
signaling promotes transcription of both twist and repressor of
twist. (B) Notch acts permissively on the twist gene, but
instructively on a repressor of twist gene. repressor of
twist [E(spl)-C] transcription requires Nicd to
alleviate Su(H)-mediated repression and to serve as a coactivator for Su(H).
twist transcription is dependent on Nicd, as well as other
factors. Nicd is solely required to de-repress Su(H). Su(H) bound
to other coactivators and/or other transcriptional activators is necessary for
twist activation.
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