|
| Status |
Public on Apr 01, 2020 |
| Title |
Transient Transcriptome Sequencing (TT-seq) of Nascent Gene Expression upon BRD4-NUT Protein Degradation/Recovery and RNA Polymerase II Inhibition |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Delineating how chromosomes fold at length scales beyond one megabase remains obscure relative to smaller-scale folding into TADs, loops, and nucleosomes. We find that rather than simply unfolding chromatin, histone hyperacetylation results in interactions between distant genomic loci separated by tens to hundreds of megabases, even in the absence of transcription. These hyperacetylated “megadomains” are formed by the BRD4-NUT fusion oncoprotein, interact both within and between chromosomes, and form a specific nuclear subcompartment that has elevated gene activity with respect to other subcompartments. Pharmacological degradation of BRD4-NUT results in collapse of megadomains and attenuation of the interactions between them. In contrast, these interactions persist and contacts between newly acetylated regions are formed after inhibiting RNA polymerase II initiation. Our structure-function approach thus reveals that broad chromatin domains of identical biochemical composition, independent of transcription, form nuclear subcompartments, and also indicates the potential of altering chromosome structure
for treating human disease.
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|
| Overall design |
Transient transcriptome sequencing (TT-seq) to assess nascent gene expression in TC-797 cells after MZ1 treatment to degrade BRD4-NUT, after MZ1 treatment followed by drug washout to partially restore BRD4-NUT protein levels, and after triptolide treatment to inhibit RNA polymerase II transcription.
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| |
|
| Contributor(s) |
Eagen KP |
| Citation(s) |
32243828 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| DP5 OD024587 |
Biochemical Basis of Chromatin Folding and Chromosome Condensation |
NORTHWESTERN UNIVERSITY AT CHICAGO |
Kyle Patrick Eagen |
|
| Submission date |
Jun 21, 2019 |
| Last update date |
Jul 01, 2020 |
| Contact name |
Kyle Eagen |
| E-mail(s) |
kyle.eagen@bcm.edu
|
| Organization name |
Baylor College of Medicine
|
| Department |
Department of Molecular and Cellular Biology
|
| Lab |
Eagen Lab
|
| Street address |
1 Baylor Plaza
|
| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77030 |
| Country |
USA |
| |
|
| Platforms (1) |
|
| Samples (13)
|
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| This SubSeries is part of SuperSeries: |
| GSE133165 |
Chromatin Hyperacetylation Impacts Chromosome Folding by Forming a Nuclear Subcompartment |
|
| Relations |
| BioProject |
PRJNA550127 |
| SRA |
SRP202552 |
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