Journal of biological rhythmsDec 1, 2025

TRITHORAX and HSP68 may influence the transcription of clock genes in the feedback loop of Drosophila.

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jan 2, 2026

Abstract

Monarch and Drosophila share similar mechanisms for circadian clock regulation, with CLK activation being well-conserved.

The circadian clock in eukaryotes relies on transcriptional feedback loops.
In both monarchs and Drosophila, components like CLKe19r, TRX, and HSP68 are essential for CLK activation.
HSP68 is necessary for PER repression in Drosophila, but methylation of HSP68 at R45 is not required.
These findings suggest that while CLK activation mechanisms are conserved, PER repression may differ between species.
This study highlights the complexity of circadian regulation and the potential for varied mechanisms across different organisms.

Simplified

The circadian clock in eukaryotes keeps time via transcriptional feedback loops. In the transcriptional feedback loop of animals, CLOCK activator complexes drive expression of PER repressor complex components which feedback to inhibit CLOCK activation until PER complexes are degraded, thus initiating the next round of CLOCK activation ~24 h later. Recently, we showed that a region of monarch CLOCK (CLK) analogous to that encoded by mammalian CLOCK exon 19 (CLKe19r) and the methyltransferase TRITHORAX (TRX) are required for CLK activation, PER-CLK binding, and PER repression and that TRX-dependent methylation of Heat Shock Protein 68 (HSP68) at arginine 45 (R45) is necessary for PER-CLK binding and PER repression. Given that CLK activation and PER repression complexes in Drosophila are comprised of different core components than in monarchs, we tested whether similar mechanisms are used for CLK activation and PER repression in Drosophila. We found that the CLKe19r, TRX and HSP68 are all required for CLK activation yet only HSP68, but not HSP68 R45 methylation, is required for PER repression in Drosophila. These results reveal a well-conserved CLK activation mechanism and a PER repression mechanism that retains HSP68 function but does not require TRX-dependent methylation.

Full Text

Full text is available at the source.

View Full Text ↗

Funding

Competing interests

Conflict of Interest StatementThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Christine Merlin and Paul E. Hardin are members of the Editorial Board of Journal of Biological Rhythms . The authors did not take part in the peer review or decision-making process for this submission and has no further conflicts to declare.

PubMed

TRITHORAX and HSP68 may influence the transcription of clock genes in the feedback loop of Drosophila.

Abstract

Full Text

Funding

Competing interests

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the circadian biology brief

Abstract

Full Text

Funding

Competing interests

Related papers

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the circadian biology brief