# The Role of Parental Histone Proteins in Early Development

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $38,717

## Abstract

Abstract
Oocytes and sperm are terminally differentiated cells that can give rise to a multicellular organism after
fertilization despite using an identical genetic template. How this happens has intrigued biologists for decades
and has helped spur advancements in the understanding of the cellular epigenome. The epigenome is comprised
of several types of chemical modifications on either histone proteins or the DNA itself. Collectively, these
epigenetic modifications stabilize gene expression patterns and establish cellular identity. In somatic cells these
epigenetic states are maintained through many mitotic divisions, but are largely cleared in the germline and early
embryos to ensure proper development, and/ or prevent the inheritance of acquired epigenetic information
across generations. Despite the two waves of genome-wide reprogramming in embryos and germ cells,
inheritance of non-genetic information has been observed in various organisms including humans. These
observations have raised fundamental questions - Do gametes convey epigenetic information to the zygote?
What is the molecular nature of an epigenetic carrier across generations? A logical and reasonable carrier of
epigenetic memory are histone proteins, but whether the parental histones are physically inherited or have a
functional role in embryonic development remains unknown due to technical and experimental limitations.
Therefore, to overcome these challenges we have developed cutting edge genetic and molecular tools to
visualize and track maternal and paternal histones in the early embryo and during the first few divisions. Based
on previous literature and my preliminary data, I hypothesize that maternal and paternal histones are retained in
the zygote, and persist across multiple embryonic cell divisions. To address these questions, I will use a
combination of mouse genetics, early embryonic manipulations, immunohistochemical, single-molecule
resolution imaging techniques. These studies will provide fundamental insights into whether histones can serve
as informational carriers of epigenetic memory. Additionally, completion of this work will provide me with critical
scientific and technical training, as outlined in my training plan, which will be foundational for a successful career
as an independent scientist studying the core principles that dictate our early development.

## Key facts

- **NIH application ID:** 10240661
- **Project number:** 5F31HD100124-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Gabriel Lee Manske
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,717
- **Award type:** 5
- **Project period:** 2019-09-04 → 2022-09-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240661

## Citation

> US National Institutes of Health, RePORTER application 10240661, The Role of Parental Histone Proteins in Early Development (5F31HD100124-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10240661. Licensed CC0.

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