Delay in Feedback Repression by Cryptochrome 1 Is Required for Circadian Clock Function

@article{UkaiTadenuma2011DelayIF,
  title={Delay in Feedback Repression by Cryptochrome 1 Is Required for Circadian Clock Function},
  author={Maki Ukai-Tadenuma and Rikuhiro G. Yamada and Haiyan Xu and J{\"u}rgen A. Ripperger and Andrew C. Liu and Hiroki R. Ueda},
  journal={Cell},
  year={2011},
  volume={144},
  pages={268-281}
}
Direct evidence for the requirement of delay in feedback repression in the mammalian circadian clock has been elusive. Cryptochrome 1 (Cry1), an essential clock component, displays evening-time expression and serves as a strong repressor at morning-time elements (E box/E' box). In this study, we reveal that a combination of day-time elements (D box) within the Cry1-proximal promoter and night-time elements (RREs) within its intronic enhancer gives rise to evening-time expression. A synthetic… Expand
Mammalian circadian clock: the roles of transcriptional repression and delay.
TLDR
Experimental verification of the roles of each motif as well as post-transcriptional regulation of the circadian oscillator will be the next challenges. Expand
Dual modes of CLOCK:BMAL1 inhibition mediated by Cryptochrome and Period proteins in the mammalian circadian clock.
TLDR
A new model for the mammalian circadian clock is proposed in which the negative arm of the TTFL proceeds by two different mechanisms during the circadian cycle, and it is proposed that CRY is the primary repressor in this model. Expand
Accurate timekeeping is controlled by a cycling activator in Arabidopsis
TLDR
It is demonstrated that a related Myb-like protein, REVEILLE8 (RVE8), is a direct transcriptional activator of EE-containing clock and output genes, suggesting that the plant clock consists of a highly interconnected, complex regulatory network rather than of coupled morning and evening feedback loops. Expand
CRYPTOCHROMES confer robustness, not rhythmicity, to circadian timekeeping
TLDR
It is suggested that, whereas circadian transcriptional feedback imparts robustness and functionality onto biological clocks, the core timekeeping mechanism is post-translational, and PER proteins normally act as signalling hubs that transduce timing information to the nucleus, imparting daily rhythms upon the activity of transcriptional effectors. Expand
Emerging Models for the Molecular Basis of Mammalian Circadian Timing
TLDR
High-resolution structures of core circadian transcriptional regulators are analyzed and biochemical data is integrated to suggest how remodeling of clock protein complexes may be achieved throughout the 24 h cycle. Expand
CRYPTOCHROMES confer robustness, not rhythmicity, to circadian timekeeping
TLDR
It is suggested that, whereas circadian transcriptional feedback imparts robustness and functionality onto biological clocks, the core timekeeping mechanism is post‐translational. Expand
Transcription-based circadian mechanism controls the duration of molecular clock states in response to signaling inputs.
TLDR
A possible mechanism for clock-controlled metabolic homeostasis is revealed, whereby the circadian clock controls the relative duration of different molecular (and metabolic) states in response to signaling inputs. Expand
A mammalian circadian clock model incorporating daytime expression elements.
TLDR
This model reproduces predictions concerning the dual regulation of Cry1 by the D-box and Rev-ErbA/ROR response element (RRE) promoter elements and allows for ensemble-based predictions of phase response curves (PRCs). Expand
Identification of a Novel Cryptochrome Differentiating Domain Required for Feedback Repression in Circadian Clock Function*
TLDR
It is demonstrated, through cell-based genetic complementation and real-time molecular recording, that Cry1 alone is able to maintain cell-autonomous circadian rhythms, whereas Cry2 cannot, and a cryptochrome differentiating α-helical domain within the photolyase homology region of CRY1, designated asCRY1-PHR(313–426), that is required for clock function and distinguishes CRy1 from CRY2. Expand
Protein dynamics regulate distinct biochemical properties of cryptochromes in mammalian circadian rhythms
TLDR
A dynamic loop in the secondary pocket that regulates differential binding of cryptochromes to the PAS domain core of CLOCK:BMAL1 is identified and identified as a key biochemical and structural difference between CRY1 and CRY2 that underlies their differential strengths as transcriptional repressors. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 57 REFERENCES
Cry1 Circadian Phase in vitro: Wrapped Up with an E-Box
TLDR
The results suggest that, at least in this in vitro model of the clock, RORE are not necessary for the appropriate circadian regulation of Cry1 expression and rather suggest that sequences surrounding the proximal E-boxes confer gene-specific circadian phasing. Expand
Feedback repression is required for mammalian circadian clock function
TLDR
It is demonstrated that CRY-mediated repression of the CLOCK/BMAL1 complex activity is required for maintenance of circadian rhythmicity and formal proof that transcriptional feedback is requiredFor mammalian clock function is provided. Expand
Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms
TLDR
It is shown that mice lacking the Cry1 or Cry2 protein display accelerated and delayed free-running periodicity of locomotor activity, respectively, which suggests that, in addition to a possible photoreceptor and antagonistic clock-adjusting function, both proteins are essential for the maintenance of circadian rhythmicity. Expand
Cycling of CRYPTOCHROME Proteins Is Not Necessary for Circadian-Clock Function in Mammalian Fibroblasts
TLDR
It is demonstrated that cycling of CRY1, CRY2, and BMAL1 is not necessary for circadian-clock function in fibroblasts, which is not supportive of the current version of the transcription and translation feedback-loop model of the mammalian clock mechanism. Expand
A transcription factor response element for gene expression during circadian night
TLDR
The role of the Rev-ErbA/ROR response element in gene expression during circadian night is demonstrated, which is in phase with Bmal1 and in antiphase to Per2 oscillations. Expand
Rhythmic histone acetylation underlies transcription in the mammalian circadian clock
TLDR
It is shown that transcriptional regulation of the core clock mechanism in mouse liver is accompanied by rhythms in H3 histone acetylation, and that H3 acetylations is a potential target of the inhibitory action of Cry. Expand
Rhythmic PER abundance defines a critical nodal point for negative feedback within the circadian clock mechanism.
TLDR
It is demonstrated that rhythmic levels of PER2, rather than CRY1, are critical for circadian oscillations in cells and in the intact organism, and biochemical evidence supports an elegant mechanism for the disparity. Expand
A noncanonical E-box enhancer drives mouse Period2 circadian oscillations in vivo.
TLDR
The mouse mPer2 promoter is analyzed and a circadian enhancer (E2) with a noncanonical 5'-CACGTT-3' E-box located 20 bp upstream of the m per2 transcription start site is identified, sufficient to drive self-sustained circadian rhythms of luciferase activity in central and peripheral tissues from mPer 2-E2::Luciferase transgenic mice with tissue-specific phase and period characteristics. Expand
Light-independent role of CRY1 and CRY2 in the mammalian circadian clock.
TLDR
Mammalian CRY1 and CRY2 are shown to act as light-independent inhibitors of CLOCK-BMAL1, the activator driving Per1 transcription and probably regulate Per 1 transcriptional cycling by contacting both the Activator and its feedback inhibitors. Expand
System-level identification of transcriptional circuits underlying mammalian circadian clocks
TLDR
The results indicate that circadian transcriptional circuits are governed by two design principles: regulation of E/E′ boxes and RevErbA/ROR binding elements follows a repressor-precedes-activator pattern, resulting in delayed transcriptional activity, whereas regulation of DBP/E4BP4 binding elements following a repression-antiphasic-to-activators mechanism, which generates high-amplitude transcriptionalactivity. Expand
...
1
2
3
4
5
...