# Regulation and function of H2A.Z during the mid-blastula transition

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2024 · $327,789

## Abstract

PROJECT SUMMARY
Developmental progression from cleavage phase to gastrulation occurs during the mid-blastula
transition (MBT). This transition coincides with several critical events, including maternal to
zygotic transition, zygotic genome activation (ZGA), and stem cell formation. How the zygotic
genome becomes activate and how proper developmental timing is regulated are critical
unknowns in biology. Recent data in zebrafish and Drosophila indicate that these processes are
highly sensitive to the levels a particular histone, the histone variant H2A.Z (H2Av in
Drosophila). However, it remains largely unknown why altered H2A.Z levels disrupt MBT events
and how the embryo ordinarily assures that the correct amount of H2A.Z is incorporated into
chromatin. Preliminary observations indicate that in both species a subset of zygotic genes is
prematurely activated when H2A.Z levels are elevated. A combination of genomics approaches
and expression analysis of candidate genes will be used to determine the temporal pattern of
gene activation in embryos with up- or downregulated nuclear H2A.Z levels. It will also be tested
to what extent the observed changes are due to chromatin associated factors (in particular the
pattern of H2A.Z distribution across the genome) and epigenetic marks. Use of the two distinct
model systems will reveal to what extent the underlying mechanisms are conserved between
vertebrates and insects. In Drosophila, it is known that H2A.Z levels in the nucleus can be
regulated by the H2A.Z binding protein Jabba that sequesters H2A.Z in the cytoplasm, a
process active during the time of the MBT. Preliminary studies have led to the hypothesis that a
different H2A.Z-binding protein plays an analogous role in zebrafish. This hypothesis will be
tested using live imaging, embryo injections, and structure-function analysis. Successful
completion of this project will define the role of H2A.Z in controlling gene expression patterns
and in cellular programming during one of the most crucial periods of development, the mid-
blastula transition.

## Key facts

- **NIH application ID:** 10809734
- **Project number:** 5R01HD105489-03
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Patrick J. Murphy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $327,789
- **Award type:** 5
- **Project period:** 2022-07-04 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10809734

## Citation

> US National Institutes of Health, RePORTER application 10809734, Regulation and function of H2A.Z during the mid-blastula transition (5R01HD105489-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10809734. Licensed CC0.

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