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Updated: Aug 1, 2025
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An Integrated Platform for Genome-wide Mapping of Chromatin States Using High-throughput ChIP-sequencing in Tumor Tissues
Published on: April 5, 2018
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Cell state-dependent chromatin targeting in NUT carcinoma
Artyom A Alekseyenko1,2,3, Barry M Zee1,2,4, Zuzer Dhoondia1,2
1Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Genetics
|April 29, 2023
Summary
The initial cell state critically determines where BRD4-NUT fusion protein forms large, aberrant chromatin megadomains. This finding helps explain the varied patterns observed in NUT carcinoma, a cancer driven by chromatin dysregulation.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Aberrant transcriptional programming and chromatin dysregulation are hallmarks of cancer.
- The oncogenic fusion protein BRD4-NUT drives aggressive NUT carcinoma by altering chromatin regulation and c-MYC expression.
Purpose of the Study:
- To investigate the factors determining the location of BRD4-NUT-induced megadomains.
- To understand the role of cellular state in chromatin misregulation in NUT carcinoma.
Main Methods:
- Expressing BRD4-NUT in human stem cells across different differentiation states.
- Analyzing the formation patterns of hyperacetylated genomic megadomains.
- Investigating c-MYC protein-protein interactions in patient-derived cell lines.
Main Results:
- Megadomain formation patterns differed significantly between pluripotent and mesodermally induced stem cells.
- Initial cell state, not just genome sequence, dictates megadomain locations.
- Analysis supports a cascade of chromatin misregulation in NUT carcinoma.
Conclusions:
- The initial epigenetic cell state is the critical determinant for BRD4-NUT megadomain localization.
- These findings provide insights into the chromatin-based mechanisms driving NUT carcinoma.
- Understanding these mechanisms may open new therapeutic avenues for this aggressive cancer.
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