# A novel epigenetic mechanism in early embryogenesis

> **NIH NIH R35** · YALE UNIVERSITY · 2021 · $459,966

## Abstract

Mammalian early embryogenesis is a fundamental question in biology. Recent studies
have demonstrated that global remodeling of chromatin structure plays a critical role in acquiring
and maintaining toti- or pluri-potency. Although their exact function remains elusive,
endogenous transposable elements (TEs), remnants of ancient transposons, are associated
with dynamic chromatin remodeling in early embryogenesis. Furthermore, although trophoblast
stem cells (TSCs) play essential roles in supporting embryonic development, little is known
about their chromatin structure. TEs plays an essential role in the acquirement of placenta in
eutherians during evolution. Intriguingly, the specification of the trophoblast lineage occurs when
traditional epigenetic marks reaches the lowest point, indicative of the existence of novel
mechanisms.
 DNA methylation is a critical factor in the regulation of chromatin structures. A series of
recent studies, including ours, have discovered a novel type of DNA methylation, N6-
methyladenine (N6-mA), in metazoans. In general, N6-mA is expressed at very low levels in
adult mammalian tissues and can be upregulated under environmental stress or in
tumorigenesis. N6-mA levels are greatly elevated in early embryogenesis in various metazoans,
including mammals. Interestingly, we and others also demonstrated the specific role of N6-mA
in silencing TEs in mouse embryonic stem cells, brains and human tumor cells. Our most
recent results demonstrated a surprising function of N6-mA in promoting dynamic chromatin
structures in stem cells thereby promoting the stem cell fate (TSCs), via stabilizing DNA
secondary structure at TEs. This proposal aims to further investigate this novel mechanism.
The outcome of this proposal will pave the way to a new research direction in epigenetics and
embryogenesis.

## Key facts

- **NIH application ID:** 10127676
- **Project number:** 5R35GM136346-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** zhuo Andrew Xiao
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $459,966
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10127676

## Citation

> US National Institutes of Health, RePORTER application 10127676, A novel epigenetic mechanism in early embryogenesis (5R35GM136346-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10127676. Licensed CC0.

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