C-Jun recruits the NSL complex to regulate its target gene expression by modulating H4K16 acetylation and promoting the release of the repressive NuRD complex

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-speci...

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Published inOncotarget Vol. 6; no. 16; pp. 14497 - 14506
Main Authors Liu, Yan, Long, Yuehong, Xing, Zhaobin, Zhang, Daoyong
Format Journal Article
LanguageEnglish
Published United States Impact Journals LLC 10.06.2015
Subjects
Acetylation
Cell Differentiation
Cell Line, Tumor
Cell Proliferation
Gene Expression Regulation
HEK293 Cells
Humans
Mi-2 Nucleosome Remodeling and Deacetylase Complex - genetics
Mi-2 Nucleosome Remodeling and Deacetylase Complex - metabolism
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Phosphorylation
Proto-Oncogene Proteins c-jun - genetics
Proto-Oncogene Proteins c-jun - metabolism
Research Paper
Transcription Factors - metabolism
Transfection
H4K16 acetylation
NSL complex
C-Jun
phosphorylation
NuRD complex
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Summary: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.
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ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.3988