# Mechanisms of Epigenetic inheritance

> **NIH NIH R35** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $24,167

## Abstract

How epigenetic states are inherited during S phase of the cell cycle is one of the most challenging questions in
the chromatin and epigenetic fields. DNA replication-coupled nucleosome assembly plays an important role in
epigenetic inheritance following DNA replication and DNA repair. Mutations of most, if not all, genes involved in
replication-coupled nucleosome assembly result in defects in transcriptional silencing at heterochromatin and
genome instability in both yeast and mammalian cells. We have been studying how nucleosomes are formed
following DNA replication in yeast and human cells and have made multiple significant contributions to this
process. However, how parental histone (H3-H4)2 tetramers are transferred to replicating DNA is still poorly
understood, which hinders our understanding of transmission of epigenetic information into daughter cells. The
major challenge to understanding parental histone (H3-H4)2 assembly is a lack of methods to track this
process. Despite this challenge, we have developed the eSPAN (enrichment and Sequencing Protein-
Associated Nascent DNA) method that can discern whether a protein binds to leading or lagging strands of
DNA replication forks. This method enables us for the first time to monitor nucleosome assembly of both newly
synthesized and parental histone (H3-H4)2 onto leading and lagging strands of DNA replication forks. In this
proposal, we will elucidate molecular mechanisms whereby parental (H3-H4)2 are assembled into
nucleosomes following DNA replication and how epigenetic marks are inherited during mitotic cell division in
both yeast and human cells using a combination of genetic, biochemical and genomic approaches. Together,
our studies should have a profound impact on the understanding of nucleosome assembly and epigenetic
inheritance.

## Key facts

- **NIH application ID:** 10157025
- **Project number:** 3R35GM118015-05S1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Zhiguo Zhang
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $24,167
- **Award type:** 3
- **Project period:** 2016-09-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10157025

## Citation

> US National Institutes of Health, RePORTER application 10157025, Mechanisms of Epigenetic inheritance (3R35GM118015-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10157025. Licensed CC0.

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