The Oncoprotein BRD4-NUT Generates Aberrant Histone Modification Patterns.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27698495.
- Also identified by DOI 10.1371/journal.pone.0163820 and PMC identifier 5047744.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Carcinoma, Squamous Cell
- DNA Methylation
- Histones
- Nuclear Proteins
- Oncogene Proteins, Fusion