# Epigenetic and developmental regulation of embryonic plasticity and gametogenesis

> **NIH NIH K99** · JOHNS HOPKINS UNIVERSITY · 2020 · $98,261

## Abstract

Project Summary/Abstract: Early embryonic cells are pluripotent, possessing the transient capacity to
generate all the cells of an organism. A fundamental question in developmental biology concerns identifying
the epigenetic factors that underlie this temporary developmental plasticity, as well as understanding how
commitment to a specific cell lineage is achieved and maintained. How embryonic pluripotency is established,
and whether development coordinates the restriction of cellular plasticity with the acquisition of cell fate is
poorly understood. Epigenetic phenomena refer to changes in gene expression and chromatin organization
inherited through cell divisions without changing the underlying DNA sequences. Recently, studies during my
postdoctoral research have uncovered an unappreciated developmental regulation of the incorporation of key
molecular carriers of epigenetic information, the replication-coupled histone H3 and histone variant, H3.3,
during gametogenesis that influences the epigenetic organization in the early embryo, with a lasting effect on
pluripotency and lineage commitment.
 The goal of this Pathway to Independence Award proposal is to request support for training in order to
develop expertise in, and to apply, genomic approaches while addressing the role of epigenetic regulation of
plasticity during early embryonic development, as well as cell fate maintenance. K99/R00 support during this
stage of my career will be transformative to my successful development as an independent researcher. The
research plans and career development outlined in this proposal will take advantage of the extensive
resources at Johns Hopkins University, as well as collaborate with leading experts in genomics and
bioinformatics. This proposal will examine the epigenetic regulation and developmental timing of early
embryonic plasticity. Specifically, during the K99 mentored phase of this award the principal investigator (PI)
will combine current expertise and preliminary results generated during postdoctoral training at Johns Hopkins
University, with newly developed techniques developed in the collaborator's laboratories to answer
fundamental questions regarding the dynamic epigenetic mechanisms underlying embryonic plasticity and cell
fate restriction. This approach promises to resolve the following specific aims 1) determine the developmental
significance of H3 and H3.3 bimodal incorporation during early embryogenesis and gametogenesis, 2)
characterize the genome-wide localization of H3, H3.3, and their post-translational modifications during early
embryogenesis, as well as their influence on chromatin accessibility and gene expression and 3) delineate the
molecular pathways that orchestrate the developmental regulation of two distinct classes of histone genes
important for fertility and cell fate restriction. The completion of this training will develop my research expertise,
while delineating the mechanisms underlying the epigenetic regulation of ...

## Key facts

- **NIH application ID:** 10004696
- **Project number:** 5K99HD096053-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Ryan Joseph Gleason
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $98,261
- **Award type:** 5
- **Project period:** 2019-08-29 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004696

## Citation

> US National Institutes of Health, RePORTER application 10004696, Epigenetic and developmental regulation of embryonic plasticity and gametogenesis (5K99HD096053-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10004696. Licensed CC0.

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