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Updated: Apr 12, 2026

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
C-Jun recruits the NSL complex to regulate its target gene expression by modulating H4K16 acetylation and promoting
Yan Liu1, Yuehong Long1, Zhaobin Xing1
1College of Life Sciences, Hebei United University, Tangshan, China.
Abstract:
The proto-oncogene c-Jun plays essential roles in various cellular processes, including cell proliferation, cell differentiation, and cellular apoptosis. Enormous efforts have been made to understand the mechanisms regulating c-Jun activation. The males absent on the first (MOF)-containing non-specific lethal (NSL) complex has been shown to positively regulate gene expression. However, the biological function of the NSL complex is largely unknown. Here we present evidence showing that c-Jun recruits the NSL complex to c-Jun target genes upon activation. The NSL complex catalyzes H4K16 acetylation at c-Jun target genes, thereby promoting c-Jun target gene transcription. More interestingly, we also found that the NSL complex promotes the release of the repressive NuRD complex from c-Jun target genes, thus activating c-Jun. Our findings not only reveal a new mechanism regulating c-Jun activation, but also identify the NSL complex as a c-Jun co-activator in c-Jun-regulated gene expression, expanding our knowledge of the function of the NSL complex in gene expression regulation.
Insights
The non-specific lethal (NSL) complex acts as a c-Jun co-activator, promoting gene transcription by catalyzing H4K16 acetylation and releasing the NuRD complex at target genes.
Area of Science:
- Molecular Biology
- Gene Regulation
- Epigenetics
Background:
- The proto-oncogene c-Jun is crucial for cell proliferation, differentiation, and apoptosis.
- The males absent on the first (MOF)-containing non-specific lethal (NSL) complex is known to positively regulate gene expression.
- The precise biological functions of the NSL complex remain largely uncharacterized.
Purpose of the Study:
- To elucidate the role of the NSL complex in c-Jun-mediated gene expression.
- To identify novel mechanisms regulating c-Jun activation.
- To expand the understanding of NSL complex functions in gene regulation.
Main Methods:
- Investigating the recruitment of the NSL complex to c-Jun target genes.
- Analyzing the impact of NSL complex on H4K16 acetylation.
- Assessing the effect of the NSL complex on NuRD complex release.
Main Results:
- c-Jun recruits the NSL complex to its target genes upon activation.
- The NSL complex catalyzes H4K16 acetylation at c-Jun target genes, enhancing transcription.
- The NSL complex facilitates the release of the repressive NuRD complex from c-Jun target genes.
Conclusions:
- The NSL complex functions as a c-Jun co-activator.
- NSL complex-mediated H4K16 acetylation and NuRD complex release are key mechanisms in c-Jun target gene activation.
- This study reveals a new regulatory pathway for c-Jun activation and expands the known functions of the NSL complex.
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