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Evolutionary conserved NSL complex/BRD4 axis controls transcription activation via histone acetylation
Aline Gaub1, Bilal N Sheikh1, M Felicia Basilicata1
1Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108, Freiburg, Germany.
Nature Communications
|May 9, 2020
Summary
The Non-Specific Lethal (NSL) complex and BRD4 protein collaborate to regulate gene expression. This partnership is crucial for cellular homeostasis and understanding diseases like Koolen-de Vries syndrome.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Cellular homeostasis depends on complex gene regulatory networks.
- The Non-Specific Lethal (NSL) complex is a key transcriptional regulator.
- NSL complex dysfunction, via KANSL1 haploinsufficiency, causes Koolen-de Vries syndrome.
Purpose of the Study:
- To identify co-factors of the NSL complex.
- To elucidate the functional relationship between the NSL complex and identified co-factors.
- To understand the role of this interaction in cellular homeostasis and disease.
Main Methods:
- Genome-wide RNA interference (RNAi) screen in Drosophila.
- Characterization of protein recruitment hierarchy using Drosophila and mouse embryonic stem cells.
- Transcriptome analysis of patient-derived fibroblasts.
Main Results:
- BRD4, a BET protein, was identified as an evolutionarily conserved co-factor of the NSL complex.
- A recruitment hierarchy was established: NSL-deposited histone acetylation facilitates BRD4 recruitment.
- This axis regulates the transcription of constitutively active genes.
- Koolen-de Vries patient cells show cellular homeostasis perturbations linked to the NSL complex/BRD4 axis.
Conclusions:
- BRD4 acts as a conserved bridge between the NSL complex and transcription activation.
- This interaction is vital for maintaining cellular homeostasis.
- Dysregulation of the NSL complex/BRD4 axis offers insights into Koolen-de Vries syndrome pathogenesis.
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