The Phospho-Code Determining Circadian Feedback Loop Closure and Output in Neurospora.
ARNTL Transcription Factors
/ genetics
Circadian Rhythm
/ genetics
DNA-Binding Proteins
/ genetics
Feedback, Physiological
Fungal Proteins
/ genetics
Gene Expression Regulation, Fungal
Neurospora crassa
/ genetics
Phosphorylation
Promoter Regions, Genetic
/ genetics
Signal Transduction
/ genetics
Transcription Factors
/ genetics
C-box
DNA binding
FRQ
WC-1
WC-2
ccgs
clock-controlled genes
feedback loop
frq transcription
phosphorylation
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
16 05 2019
16 05 2019
Historique:
received:
14
09
2018
revised:
07
01
2019
accepted:
01
03
2019
pubmed:
8
4
2019
medline:
17
10
2019
entrez:
8
4
2019
Statut:
ppublish
Résumé
In the negative feedback loop driving fungal and animal circadian oscillators, negative elements (FREQUENCY [FRQ], PERIODS [PERs], and CRYPTOCHROMES [CRYs]) are understood to inhibit their own expression, in part by promoting the phosphorylation of their heterodimeric transcriptional activators (e.g., White Collar-1 [WC-1]-WC-2 [White Collar complex; WCC] and BMAL1/Circadian Locomotor Output Cycles Kaput [CLOCK]). However, correlations between heterodimer activity and phosphorylation are weak, contradictions exist, and mechanistic details are almost wholly lacking. We report mapping of 80 phosphosites on WC-1 and 15 on WC-2 and elucidation of the time-of-day-specific code, requiring both a group of phosphoevents on WC-1 and two distinct clusters on WC-2, that governs circadian repression, leading to feedback loop closure. Combinatorial control via phosphorylation also governs rhythmic WCC binding to the promoters of clock-controlled genes mediating the essential first step in circadian output, a group encoding both transcription factors and signaling proteins. These data provide a basic mechanistic understanding for fundamental events underlying circadian negative feedback and output, key aspects of circadian biology.
Identifiants
pubmed: 30954403
pii: S1097-2765(19)30177-7
doi: 10.1016/j.molcel.2019.03.003
pmc: PMC6583785
mid: NIHMS1525557
pii:
doi:
Substances chimiques
ARNTL Transcription Factors
0
DNA-Binding Proteins
0
Fungal Proteins
0
Transcription Factors
0
wc-1 protein, Neurospora crassa
0
white collar 2 protein, Neurospora
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
771-784.e3Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM118021
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM118022
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM119455
Pays : United States
Organisme : NIH HHS
ID : S10 OD016212
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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