# The Role of Asymmetric Histone Inheritance in Establishing Distinct Cell Identities

> **NIH NIH F31** · JOHNS HOPKINS UNIVERSITY · 2022 · $35,204

## Abstract

Project Summary
 Cells are required to divide and organize into tissues. One method of tissue homeostasis is the utilization of adult
stem cells that are able to replace cells by undergoing asymmetric cell division (ACD) to produce a renewed stem cell and
a differentiating cell. Disruptions to this division can lead to cancers or tissue degeneration. Although ACD is a vital part
of tissue homeostasis, the underlying mechanisms involved in specifying two unique cell identities during this process are
unknown. Previous work studying the epigenetic mechanisms of ACD in the Drosophila male germline found that, by
labeling old and new histones distinctively, old H3 histones are retained in the renewed stem cell, whereas new H3 histones
are preferentially segregated to the differentiating cell.
 To investigate whether asymmetric histone inheritance is an important mechanism of ACD, I will study histone
inheritance in the intestinal stem cells (ISCs) of Drosophila. The ISCs undergo ACD to produce two differentiated cell
types, enterocyte and enteroendocrine cells. The ISCs are also able to undergo symmetric cell division (SCD) to produce
two ISCs. The ISC lineage is ideal to study histone inheritance as it is high throughput as there are many ISCs in one
intestine, the ISC is the only cell in the lineage to undergo mitosis, and transgenes can be expressed in only the progenitor
cells. I will take advantage of a two-color transgenic system to label old and new histones differentially and track their
segregation during ISC division. My preliminary data suggest that H3 histones are segregated asymmetrically during the
ACD of ISCs, while H3 histones are segregated symmetrically during SCD. In contrast, H2A histones are segregated
symmetrically in both ACD and SCD. This suggests that H3 may be important for establishing different cell identities.
 To investigate the cellular and molecular mechanisms of histone inheritance, I will first look at old and new histone
deposition in recently replicated sister chromatids and then study the segregation of the sister chromatids during mitosis. I
will use a chromatin fiber technique to study the incorporation of histones following DNA replication in ISCs. I will then
analyze components of the mitotic machinery that recognizes and segregates these epigenetically distinct sister chromatids
during cell division. Further, I will investigate a mutation in the tail of the H3 histone, which has been previously found to
cause aberrant histone inheritance and cellular defects such as tumors and tissue degeneration in the Drosophila germline.
 After characterizing the mechanism of H3 inheritance during cell division, I will investigate how H3 inheritance
influences cell identity. To study this, I will examine the chromatin context at gene loci that are important for cell identity
to determine if different chromatin contexts are established and inherited through cell division. I will also investigate gene
expression in a wildtyp...

## Key facts

- **NIH application ID:** 10347379
- **Project number:** 5F31DK122702-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Emily Hope Zion
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $35,204
- **Award type:** 5
- **Project period:** 2020-03-16 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10347379

## Citation

> US National Institutes of Health, RePORTER application 10347379, The Role of Asymmetric Histone Inheritance in Establishing Distinct Cell Identities (5F31DK122702-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10347379. Licensed CC0.

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