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The Oncoprotein BRD4-NUT Generates Aberrant Histone Modification Patterns.

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.

SUBMITTER: Zee BM

PROVIDER: S-EPMC5047744 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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The Oncoprotein BRD4-NUT Generates Aberrant Histone Modification Patterns.

Zee Barry M BM Dibona Amy B AB Alekseyenko Artyom A AA French Christopher A CA Kuroda Mitzi I MI

PloS one 20161003 10

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 29 ...[more]

PMID: 27698495

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miR-3140 suppresses tumor cell growth by targeting BRD4 via its coding sequence and downregulates the BRD4-NUT fusion oncoprotein.

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The oncogenic BRD4-NUT chromatin regulator drives aberrant transcription within large topological domains

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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Deciphering the Role of microRNAs in BRD4-NUT Fusion Gene Induced NUT Midline Carcinoma.

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