# The role of ZCWPW1 in meiosis

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $596,497

## Abstract

Abstract: While generation of sperm and eggs through meiosis is exquisitely coordinated and tightly regulated,
chromosome segregation is remarkably error prone. In humans it is estimated that ~5% of sperm and ~30% of
oocytes have the wrong chromosome complement - known as aneuploidy. As such, errors in meiotic
chromosome segregation are a leading cause of mental disability, miscarriage, and infertility. In mammals,
critical steps that ensure faithful chromosome segregation include generation of programmed DNA double-
stranded breaks (DSBs) at PRDM9 hotspots that are enriched for dual Histone H3 lysine 4 and lysine 36
trimethylation (K4/H3K36me3), the pairing of parental chromosomes (homologs), the co-alignment of homologs
lengthwise, and the tethering of homologs by crossing over – the exchange of chromosome arms between
homologs. Despite this wealth in knowledge, a key gap in knowledge in this process is how PRDM9-dependent
dual H3K4/H3K36me3 modifications influence homolog pairing and recombination. We and others have shown
that ZCWPW1, a dual histone methylation reader, is enriched at PRDM9 target sites, has no effect on the number
or location of DSBs, but may be important for DSB repair. More specifically, our preliminary data suggest that
ZCWPW1 may be required for efficient homolog pairing which when compromised culminates in chromosome
entanglements, DSB repair defects, and ultimately chromosome mis-segregation and infertility. Therefore, we
propose a comprehensive and integrative analysis using genetic, genomic, molecular, and biochemical
approaches to dissect the role of ZCWPW1 in homolog pairing and recombination. Overall, these studies will
provide fundamental knowledge about meiotic chromosome dynamics and a mechanistic understanding of the
role of ZCWPW1 in mammalian meiosis.

## Key facts

- **NIH application ID:** 10908447
- **Project number:** 5R01GM148028-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Francesca Cole
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $596,497
- **Award type:** 5
- **Project period:** 2023-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10908447

## Citation

> US National Institutes of Health, RePORTER application 10908447, The role of ZCWPW1 in meiosis (5R01GM148028-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10908447. Licensed CC0.

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