# Study epigenetic inheritance during development and across generations using multiple model

> **NIH NIH R35** · JOHNS HOPKINS UNIVERSITY · 2020 · $328,895

## Abstract

Title: Study epigenetic inheritance during development and across generations using multiple
model organisms
Project Summary/Abstract:
Epigenetics refers to effects on gene expression or function that are inheritable through mitosis
or meiosis without altering the primary DNA sequences. Epigenetic mechanisms play important
roles in regulating cell identity and activity. Failure in appropriate epigenetic regulation leads to
abnormal behaviors of cells, which underlies many diseases such as diabetes, muscular
dystrophy, neurodegenerative disease, infertility, and many forms of cancer.
Many types of stem cells undergo asymmetric cell divisions to give rise to two daughter cells
with distinct cell fates: a self-renewed stem cell and to another daughter cell that differentiates.
We found that during the asymmetric division of Drosophila male germline stem cell (GSC), the
preexisting histone 3 (H3) are selectively segregated to the GSC whereas newly synthesized H3
are enriched in the differentiating daughter cell. Our studies provide the first direct evidence that
stem cells retain preexisting histones during asymmetric cell divisions in vivo, which may
contribute to maintain their unique epigenetic memory.
These unprecedented discoveries have placed us at a unique position to solve a long-standing
question regarding whether and how cells maintain their epigenetic memories through many cell
divisions and across generations, which have become our major research focuses. Our current
work has three main directions: (1) to understand the molecular mechanisms and cellular basis
of asymmetric histone inheritance using Drosophila male GSC as a model system; (2) to
investigate the generality of asymmetric epigenetic inheritance in other cell types of Drosophila
and in other organisms/systems, such as C.elegans and mouse embryonic stem cells; (3) to
study intergenerational and transgenerational epigenetic inheritance in C.elegans and
Drosophila. We propose to use molecular genetics, cell biology, genomic, and biophysical
approaches in our research, which will have far-reaching impact on a broad range of fields,
including stem cell biology, chromatin biology, developmental biology, and reproductive biology.

## Key facts

- **NIH application ID:** 9922325
- **Project number:** 5R35GM127075-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Xin Chen
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $328,895
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9922325

## Citation

> US National Institutes of Health, RePORTER application 9922325, Study epigenetic inheritance during development and across generations using multiple model (5R35GM127075-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9922325. Licensed CC0.

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