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Methylome inheritance and enhancer dememorization reset an epigenetic gate safeguarding embryonic programs
Xiaotong Wu1, Hongmei Zhang1, Bingjie Zhang1
1Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Science Advances
|December 22, 2021
Summary
Global DNA methylation reprogramming differs between mammals and nonmammals. Zebrafish studies reveal enhancer dememorization safeguards embryonic gene expression, unifying distinct epigenetic reprogramming modes.
Area of Science:
- Epigenetics
- Developmental Biology
- Genomics
Background:
- Epigenetic reprogramming is crucial for early embryonic development.
- Mammals undergo global DNA demethylation post-fertilization, unlike nonmammalian vertebrates.
- Zebrafish exhibit enhancer dememorization alongside DNA methylation inheritance.
Purpose of the Study:
- To investigate the role of DNA methylation in zebrafish early development.
- To understand the mechanism behind differential epigenetic reprogramming in vertebrates.
- To explore the concept of enhancer dememorization in embryonic development.
Main Methods:
- Maternal dnmt1 depletion via oocyte microinjection in zebrafish.
- Analysis of DNA methylation, gene expression, and histone modifications (H3K4me3).
- Comparative study of embryonic and adult tissue-specific enhancers.
Main Results:
- DNA methylation deficiency in zebrafish embryos caused developmental defects and lethality.
- Methylation-deficient embryos showed derepression of adult genes and ectopic H3K4me3 at CG-rich enhancers.
- Embryonic enhancers, typically CG-poor, escaped DNA methylation repression.
Conclusions:
- Global DNA hypermethylation and enhancer dememorization create an epigenetic gate in zebrafish.
- This epigenetic mechanism ensures proper embryonic gene expression timing.
- Enhancer dememorization offers a unified explanation for distinct vertebrate epigenetic reprogramming strategies.
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