# Epigenetic mechanisms governing genome partitioning and gene expression in germ cells

> **NIH NIH R35** · YALE UNIVERSITY · 2022 · $418,180

## Abstract

Three-dimensional genome organization, in which the linear DNA sequence is partitioned into
functionally distinct domains, is essential for the precise deployment of genetic information in every cell
type. An increasing number of devastating disorders and diseases have recently been attributed to
disruption of genome organization, yet the mechanistic underpinnings remain poorly understood,
especially in vivo. In particular, how the activity of binding factors and sequence elements is translated to
epigenetic states and three-dimensional genomic domains to govern gene expression remains
mysterious. The germ line of C. elegans provides a relevant and experimentally advantageous in vivo
model to dissect the mechanisms governing proper establishment of genomic domains with coordinated
regulation. In this system, we investigate diverse large-scale gene regulatory mechanisms controlling
piRNA biogenesis, X chromosome regulation, and transformation from the germline to the somatic fate.
We have recently developed the ability to reliably purify germ nuclei at quantities sufficient for genomic
analyses, including ChIP-seq, RNA-seq, and chromatin capture conformation assays. This achievement
removes a major barrier in the field to dissect gene expression mechanisms in the germ line. With this
new capacity, we will now characterize fundamental transcriptional and epigenetic mechanisms in wild
type germ nuclei with unprecedented specificity. Using these data, we will now define key mechanisms
governing the germline-to-soma transformation, the coordinated, germline-specific regulation of genomic
domains containing thousands of piRNA genes, and the temporal and global regulation of X chromosome
gene expression in the germ line. The successful completion of the proposed experiments will illuminate
the poorly understood yet vitally important in vivo mechanisms by which large-scale genome organization
influences gene expression, and vice versa.

## Key facts

- **NIH application ID:** 10364657
- **Project number:** 5R35GM131776-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** VALERIE J REINKE
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $418,180
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364657

## Citation

> US National Institutes of Health, RePORTER application 10364657, Epigenetic mechanisms governing genome partitioning and gene expression in germ cells (5R35GM131776-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10364657. Licensed CC0.

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