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  • A circadian-like gene network programs the timing and dosage of heterochronic miRNA transcription during C. elegans development
Title: A circadian-like gene network programs the timing and dosage of heterochronic miRNA transcription during C. elegans development
Development relies on the exquisite control of both the timing and the levels of gene expression to achieve robust developmental transitions. How cis- and trans-acting factors control both aspects simultaneously is unclear. We show that transcriptional pulses of the temporal patterning microRNA (miRNA) lin-4 are gener- ated by two nuclear hormone receptors (NHRs) in C. elegans, NHR-85 and NHR-23, whose mammalian ortho- logs, Rev-Erb and ROR, function in the circadian clock. Although Rev-Erb and ROR antagonize each other to control once-daily transcription in mammals, NHR-85/NHR-23 heterodimers bind cooperatively to lin-4 reg- ulatory elements to induce a single pulse of expression during each larval stage. Each pulse’s timing, ampli- tude, and duration are dictated by the phased expression of these NHRs and the C. elegans Period ortholog, LIN-42, that binds to and represses NHR-85. Therefore, during nematode temporal patterning, an evolu- tionary rewiring of circadian clock components couples the timing of gene expression to the control of tran- scriptional dosage.  more » « less
Award ID(s):
2217560
PAR ID:
10610468
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ;
Editor(s):
Kim, John
Publisher / Repository:
Cell
Date Published:
Journal Name:
Developmental Cell
Volume:
58
Issue:
22
ISSN:
1534-5807
Page Range / eLocation ID:
2563 to 2579.e8
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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