The Catalytic and Non-catalytic Functions of the Chromatin-Remodeling Protein Collaborate to Fine-Tune Circadian Transcription in

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The circadian clock is an endogenous timing system that enables organisms to anticipate daily changes in their external environment and temporally coordinate key biological functions that are important to their survival. Central to Drosophila clockwork is a key transcription factor CLOCK (CLK). CLK activates expression of target genes only during specific parts of the day, thereby orchestrating rhythmic expression of hundreds of clock-controlled genes, which consequently manifest into daily rhythms in physiology and behavior. In this study, we demonstrated that the Brahma (Brm) chromatin-remodeling protein interacts with CLK and fine-tune the levels of CLK-dependent transcription to maintain the robustness of the circadian clock. Specifically, we uncovered two distinct but collaborative functions of Brm. Brm possesses a non-catalytic function that negatively regulates the binding of CLK to target genes and limits transcriptional output, likely by recruiting repressive protein complexes. Catalytically, Brm functions by condensing the chromatin at CLK target genes, specifically when transcription is active. This serves to precisely control the level of repressive factors likely recruited by Brm as well as other transcriptional regulators. By disentangling these two roles of Brm, our study uncovered a multi-layered mechanism in which a chromatin remodeler regulates the circadian clock.

Vyšlo v časopise: The Catalytic and Non-catalytic Functions of the Chromatin-Remodeling Protein Collaborate to Fine-Tune Circadian Transcription in. PLoS Genet 11(7): e32767. doi:10.1371/journal.pgen.1005307
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005307

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