# Elucidating how pioneer factors drive dynamic chromatin accessibility during zygotic genome activation

> **NIH NIH F31** · YALE UNIVERSITY · 2023 · $32,594

## Abstract

PROJECT SUMMARY
Dynamic remodeling of the three-dimensional organization of the genome regulates gene expression to
coordinate the healthy development of organisms and can impact disease progression when dysregulated.
Recent advances have enabled the visualization of accessible chromatin in situ in fixed samples; however, we
still do not fully understand how changes in chromatin organization occur in vivo during vertebrate
development, especially at the single-cell level. Therefore, the goal of this project is to study the dynamic
remodeling of chromatin organization during zygotic genome activation, when the transcriptionally silent
embryo first initiates transcription of its own genes and genome architecture is dramatically remodeled. First
(Aim 1), I will investigate the dynamic spatial organization of chromatin accessibility during genome activation
in zebrafish. To do so, I will use Live-ATAC, a method I recently developed. Live-ATAC enables real time
detection of chromatin accessibility in vivo at the single-cell level in living embryos. Using this method, I will
determine precisely when and where chromatin accessibility is gained as the embryo undergoes genome
activation and transcription is initiated. Second (Aim 2), I will use Live-ATAC in mutant embryos to dissect the
role of pioneer transcription factors in dynamically remodeling chromatin accessibility during genome
activation. Specifically, I will use embryos lacking functional Nanog, Oct4, and Sox19b which are maternally
supplied transcription factors have been implicated in pluripotency and genome activation. Simultaneously, I
will measure transcription of the first zygotically transcribed genes to determine the causal relationships
between transcription factors, chromatin accessibility, and transcription in real time in vivo. Altogether, this
work will provide an unprecedented view of how chromatin organization is dynamically remodeled during
cellular reprogramming and begin elucidating the underlying mechanisms. This will inform our understanding of
how three-dimensional genome organization may affect human embryogenesis and disease given the likely
conserved regulatory principles.

## Key facts

- **NIH application ID:** 10520009
- **Project number:** 5F31HD104443-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Mark Pownall
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $32,594
- **Award type:** 5
- **Project period:** 2020-11-01 → 2024-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10520009

## Citation

> US National Institutes of Health, RePORTER application 10520009, Elucidating how pioneer factors drive dynamic chromatin accessibility during zygotic genome activation (5F31HD104443-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10520009. Licensed CC0.

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