Understanding the role of chromatin remodeling in the regulation of circadian transcription inDrosophila

Mar 2, 2016Fly

How DNA packaging changes control daily gene activity in fruit flies

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Abstract

The BRAHMA protein is crucial for regulating circadian transcription in Drosophila.

Circadian clocks help organisms synchronize their physiology and behavior with the day-night cycle.
Circadian gene expression relies on transcription factor binding, RNA polymerase II activity, and post-transcriptional mechanisms.
Changes in chromatin structure, including histone modifications and nucleosome density, influence transcription factor recruitment and RNA polymerase II function.
The non-catalytic activity of BRM may recruit repressive factors to control the transcriptional output of CLOCK during active phases.
The ATP-dependent catalytic activity of BRM is proposed to adjust nucleosome density to prevent excessive recruitment of negative regulators.
Ongoing research aims to enhance understanding of how chromatin-level transcriptional regulation affects circadian gene expression.

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Circadian clocks enable organisms to anticipate daily changes in the environment and coordinate temporal rhythms in physiology and behavior with the 24-h day-night cycle. The robust cycling of circadian gene expression is critical for proper timekeeping, and is regulated by transcription factor binding, RNA polymerase II (RNAPII) recruitment and elongation, and post-transcriptional mechanisms. Recently, it has become clear that dynamic alterations in chromatin landscape at the level of histone posttranslational modification and nucleosome density facilitate rhythms in transcription factor recruitment and RNAPII activity, and are essential for progression through activating and repressive phases of circadian transcription. Here, we discuss the characterization of the BRAHMA (BRM) protein in Drosophila in the context of regulation. By dissecting its catalytic vs. non-catalytic activities, we propose a model in which the non-catalytic activity of BRM functions to recruit repressive factors to limit the transcriptional output of CLOCK (CLK) during the active phase of circadian transcription, while the primary function of the ATP-dependent catalytic activity is to tune and prevent over-recruitment of negative regulators by increasing nucleosome density. Finally, we divulge ongoing efforts and investigative directions toward a deeper mechanistic understanding of transcriptional regulation of circadian gene expression at the chromatin level.

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Understanding the role of chromatin remodeling in the regulation of circadian transcription inDrosophila

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