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The Oncoprotein BRD4-NUT Generates Aberrant Histone Modification Patterns

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5047744.pdf (1.7 MB)

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2016

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10.1371/journal.pone.0163820

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Public Library of Science
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Zee, Barry M., Amy B. Dibona, Artyom A. Alekseyenko, Christopher A. French, and Mitzi I. Kuroda. 2016. “The Oncoprotein BRD4-NUT Generates Aberrant Histone Modification Patterns.” PLoS ONE 11 (10): e0163820. doi:10.1371/journal.pone.0163820. http://dx.doi.org/10.1371/journal.pone.0163820.

Abstract

Defects in chromatin proteins frequently manifest in diseases. A striking case of a chromatin-centric disease is NUT-midline carcinoma (NMC), which is characterized by expression of NUT as a fusion partner most frequently with BRD4. ChIP-sequencing studies from NMC patients revealed that BRD4-NUT (B4N) covers large genomic regions and elevates transcription within these domains. To investigate how B4N modulates chromatin, we performed affinity purification of B4N when ectopically expressed in 293-TREx cells and quantified the associated histone posttranslational modifications (PTM) using proteomics. We observed significant enrichment of acetylation particularly on H3 K18 and of combinatorial patterns such as H3 K27 acetylation paired with K36 methylation. We postulate that B4N complexes override the preexisting histone code with new PTM patterns that reflect aberrant transcription and that epigenetically modulate the nucleosome environment toward the NMC state.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5047744/pdf/

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Biology and life sciences, Biochemistry, Proteins, DNA-binding proteins, Histones, Physical Sciences, Chemistry, Chemical Reactions, Acetylation, Biology and Life Sciences, Post-Translational Modification, Cell Biology, Chromosome Biology, Chromatin, Genetics, Epigenetics, Gene Expression, Cell biology, Chromosome biology, Chromatin modification, DNA methylation, Gene expression, DNA, DNA modification, Nucleic acids, Proteomics, Histone Acetylation, Chromatin Modification, Histone Modification, Chromatographic Techniques, Liquid Chromatography, Liquid Chromatography-Mass Spectrometry, Analytical Chemistry, Mass Spectrometry, Spectrum Analysis Techniques, Computational Biology, Genome Complexity, Genomics

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http://nrs.harvard.edu/urn-3:HUL.InstRepos:29408170

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