# Condensin connects 3D genome organization, chromosomal segregation, andgene regulation via its interactions with transcription-related factors.

> **NIH NIH R01** · UNIVERSITY OF OREGON · 2020 · $321,158

## Abstract

SUMMARY
Although disruption of 3D genome organization is connected to human diseases, including developmental
syndromes and cancer, there remain fundamental gaps in our understanding of how specific molecular
machines control genome organization. Our long-term goal is to determine how evolutionarily conserved
molecular mechanisms connect 3D genome organization and transcriptional regulation. We have recently
discovered molecular links between a key genome organizer, condensin, and the transcriptional machinery
(Mol. Cell 2015; Nature Genet. 2016). The objective here is to delineate how condensin connects 3D genome
organization, chromosomal segregation, and transcriptional regulation. The central hypothesis is that the
condensin interactions with TBP, mediator, TFIIIC and transcription factors (TFs) are required for associations
among highly transcribed (HT) genes and centromeres, which promotes faithful segregation of chromosomes
during mitosis, and that condensin controls gene transcription via 3D genome organization (gene positioning at
centromeres) or/and local chromosomal compaction. We will test our hypothesis in the highly tractable fission
yeast model (Aims 1 & 2) and characterize the more complex mechanisms in human cells using knowledge
from the yeast system (Aim 3). Under Aim 1, we will test the hypothesis that the association between HT gene
loci and centromeres, mediated by condensin-TBP interaction, is a stable structure to mediate proper
chromosomal segregation (live-cell imaging with wt and condensin mutant). We will determine how merely
positioning a gene locus at the centromere impairs transcription (lacO-based tethering). We will also test an
alternative, local mechanism, whereby condensin represses transcription of HT genes (qRT-PCR) via DNA
renaturation (nuclease assay) followed by local compaction (FISH). Under Aim 2, we will establish how
transcription-related factors (TBP, mediator, TFIIIC & TFs) contribute to condensin loading and gene
positioning at centromeres (tethering system & FISH). We will elucidate how the condensin-mediator
interaction participates in chromosomal segregation and transcriptional regulation (FISH, RNA-seq & qRT-PCR
with condensin mutant). Moreover, we will determine how the condensin interactions with TBP, mediator and
TFs organize genome-wide associations and domains (ChIA-PET & Hi-C with condensin and TF mutants).
Under Aim 3, we will use techniques from Aims 1 and 2 and condensin mutations in human RPE1 cells (in
hand), and characterize how the interaction between condensin I and hTBP is involved in (1) removal of RNA
polymerases from HT genes during mitosis and gene bookmarking; and (2) associations of HT genes and
domain formation. The innovation of this project resides in our new concept connecting condensin-mediated
3D genome organization, chromosomal segregation, and transcriptional regulation. The proposed research is
significant, because it is expected to improve the understanding of how c...

## Key facts

- **NIH application ID:** 9913556
- **Project number:** 5R01GM124195-05
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** Kenichi Noma
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $321,158
- **Award type:** 5
- **Project period:** 2017-08-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9913556

## Citation

> US National Institutes of Health, RePORTER application 9913556, Condensin connects 3D genome organization, chromosomal segregation, andgene regulation via its interactions with transcription-related factors. (5R01GM124195-05). Retrieved via AI Analytics 2026-06-07 from https://api.ai-analytics.org/grant/nih/9913556. Licensed CC0.

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