# How transcription disrupts genome 3D organization

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $36,010

## Abstract

Title:
How transcription disrupts genome 3D organization
Abstract (From parent grant, R01 GM129532):
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:** 10390097
- **Project number:** 3R01GM129523-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** SVEN W HEINZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $36,010
- **Award type:** 3
- **Project period:** 2020-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10390097

## Citation

> US National Institutes of Health, RePORTER application 10390097, How transcription disrupts genome 3D organization (3R01GM129523-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10390097. Licensed CC0.

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