# Micromechanical basis of meiotic chromosome condensation and architecture

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2022 · $438,014

## Abstract

Summary
 Chromatin folding is a key step to pack DNA molecules 10,000-fold into a germ cell, but exactly how the
meiotic chromatin is folded and how spatiotemporal folding impacts transcription, chromosome pairing, and
recombination remains largely mysterious. Homologous chromosome pairing and recombination are required
for accurate chromosome segregation. Mis-segregation of homologous chromosomes is a major cause of
miscarriage and birth defects (e.g., Down Syndrome). Three papers have recently reported that high-order
chromatin organizations/domains dynamically shape recombination landscape and germline transcriptomes.
These dramatic chromatin reorganizations depend on chromatin axes because the domain boundary proteins
(e.g., cohesins) are located in the axes. What remains unknown is 1) how meiotic chromosome axis
contributes to meiotic gene transcription, homologous chromosome pairing, and chromosome stiffness via
chromatin reorganization; and 2) whether the meiotic chromosome structure dynamics are sex- and stage-
specific. Our long-term goal is to decipher the meiotic genome organization and its roles in transcription,
homologous pairing, and recombination. The proposed work here will specifically test the overall hypothesis
that meiotic chromosome axes regulate transcriptome and homologous pairing via controlling local and global
chromatin folding in a stage- and sex- dependent manner. To test this hypothesis, we will pursue three
specific aims: Determine whether meiotic chromosome axis regulates 1) transcription and homologous
pairing via reorganizing local chromatin loops 2) chromosome stiffness and pairing by mediating global
chromatin folding. 3) Uncover the temporal and sexual differences of meiotic transcriptomes and chromatin
organization. Method: In aim 1, local chromatin reorganization in spatial domains will be detected by
chromosome conformation capture (Hi-C) contact map and the corresponding changes of transcriptional levels
within these domains can be measured via RNAseq. Chromosome interactions will be examined locally by Hi-
C analysis (aim 1) and stiffness will be measured globally by micromanipulation (aim 2). Fluorescent in situ
hybridization will be used to verify the intra- and inter-chromosome interaction found in Hi-C map. Hi-C, single-
cell RNAseq, and micromanipulation will be introduced to reveal the 4D meiotic genome reorganization and
sexual dimorphism of transcriptome and chromatin folding in aim 3. The approach is innovative because
multiple advanced methods including Hi-C, single-cell RNAseq, micromanipulation, nano-newton force
measurement, and quantitative immunocytology will be integrated to generate a more complete picture of
meiotic chromosomes. The proposed research is significant because it is expected to provide a deeper
understanding of chromosome structure and how the structure varies in different stages and genders.
Ultimately, insights from these studies will help us develop diagnosis and treatmen...

## Key facts

- **NIH application ID:** 10448366
- **Project number:** 5R01GM135549-03
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** HUANYU QIAO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $438,014
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448366

## Citation

> US National Institutes of Health, RePORTER application 10448366, Micromechanical basis of meiotic chromosome condensation and architecture (5R01GM135549-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10448366. Licensed CC0.

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