# Maternal transcription factors shaping early embryonic chromatin landscape

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA-IRVINE · 2021 · $265,247

## Abstract

Project Summary:
How the early embryonic genome – through a progressive series of epigenetic modifications controls zygotic
gene transcription, both in `time and space' – to ensure proper cellular differentiation programs, is a major
question in biology. Crucial to this process is the activity of a subset of transcription factors (TFs), which sit
high in the regulatory hierarchy to control gene expression through combinatorial interactions with cis-
regulatory modules (CRMs) that include enhancers, insulators and silencers. DNA sequence motifs present in
the CRMs of genes act as a code to dictate which genes are to be utilized at the right time, and thus activate
specific gene regulatory programs. ChIP-seq analysis of many TFs usually identifies tens of thousands of TF
binding “peaks,” genomewide, for a given cell type, but only a fraction of these sites appears to be functional. If
so, what mechanistic constrains are needed to properly regulate gene expression? These questions are
fundamentally important, but a difficult question to address in vivo using mammalian embryos due to the need
for relatively large numbers of embryos for genome-scale analyses across numerous experimental regimens.
Here we tackle this question by leveraging the strengths of the frog embryo system and examine the events of
zygotic genome activation (ZGA). As the embryo transitions from fertilized egg to pluripotent zygotic cells
giving rise to three germ layer cell fates, the embryonic genome and transcriptome need to be rapidly
reprogrammed. How can maternal TFs collectively reprogram the genome during the ZGA remains an
important area for the current research. Our recent work shows that a network of maternal TFs encoding Fox,
Sox and Pou type proteins acts through conserved mechanisms to reprogram the cellular genome into the
embryonic states. This is in part accomplished by forming enhanceososme complexes on the enhancers of
target genes, resulting in changing in histone modifications surrounding genes, and forming super enhances,
which concentrate the transcription apparatus and form phase-separated multimolecular assemblies in the
nucleus. Our premise is that maternally expressed Foxh1 and its interacting partner TFs (Sox3 and
Pou5f) function at the top of a hierarchy of TF interactions to not only mark developmental genes for
activation prior to the onset of zygotic gene expression, but also coordinate major reorganization of
the epigenetic landscape during ZGA. Through our efforts to elucidate these conserved developmental
mechanisms controlling pluripotency, our goal is to uncover the integrative roles of maternal TFs in regulating
the onset of ZGA, coordinating nucleosome phasing and histone modifications on target genes, and shaping
the 3D architecture of chromatin. We combine both genomic and imaging approaches to provide important
insights into the unifying principles that drive genome activation.
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## Key facts

- **NIH application ID:** 10086682
- **Project number:** 1R35GM139617-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Ken W.Y. Cho
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $265,247
- **Award type:** 1
- **Project period:** 2021-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10086682

## Citation

> US National Institutes of Health, RePORTER application 10086682, Maternal transcription factors shaping early embryonic chromatin landscape (1R35GM139617-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10086682. Licensed CC0.

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