# How transcription disrupts genome 3D organization

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $315,000

## Abstract

Title:
How transcription disrupts genome 3D organization
Abstract:
The 3D packaging of chromatin within the nucleus plays an important role in regulating gene expression.
While the principles of how the genome is folded in the nucleus are increasingly well understood, we know
remarkably little about the mechanisms that drive dynamic changes in genome 3D structure, e.g. during
differentiation. We recently discovered that influenza A infection inhibits transcription termination, resulting in
read-through transcription often extends hundreds of kilobases past the 3’ ends of genes. Transcription of
these regions disrupts local cohesin-mediated chromatin interactions, leads to chromatin decompaction and
frequently induces switching of previously inactive genome regions to the active compartment. These
compartment changes occur in a matter of hours, and in the absence of epigenetic changes, which usually
are found to correlate with compartment association of a locus. Further analysis of genic transcription
revealed that cohesin loss is closely temporally linked to RNA polymerase II arrival at cohesin binding sites,
suggesting that RNA polymerase II itself is involved in displacing cohesin from chromatin. To study these
phenomena in detail, we will comprehensively characterize the epigenetic and transcriptional effects of
pervasive read-through in degron-tagged cell lines as an alternative model for transcription-induced genome
3D structure changes, and test the contribution of gene structure to delimiting where RNA polymerase II
transcription changes genome organization. In a separate set of experiments, we will use a candidate
approach to identify proteins involved in transcription-associated cohesin unloading. These studies will help
reveal how transcription influences chromatin interaction and increase our knowledge of the mechanisms
that dynamically reorganize genome 3D organization.

## Key facts

- **NIH application ID:** 9888261
- **Project number:** 1R01GM129523-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** SVEN W HEINZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $315,000
- **Award type:** 1
- **Project period:** 2020-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9888261

## Citation

> US National Institutes of Health, RePORTER application 9888261, How transcription disrupts genome 3D organization (1R01GM129523-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9888261. Licensed CC0.

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