Dissecting the expression pattern during embryonic development and unveiling sustained ZGA genes with oncogenic...

Area of Science:

• Developmental Biology
• Genomics
• Computational Biology

Background:

• Zygotic genome activation (ZGA) is crucial for embryonic development, initiating gene expression post-fertilization.
• Accurately timing ZGA and identifying involved genes are significant challenges in developmental biology.

Purpose of the Study:

• To establish a computational framework for identifying ZGA genes and determining ZGA onset timing across species.
• To define a subset of Sustained ZGA (S-ZGA) genes with continuous expression post-ZGA.

Main Methods:

• Utilized time-course RNA-seq data for computational analysis.
• Developed a framework to identify ZGA-associated genes and S-ZGA genes.
• Performed epigenetic analyses (promoter accessibility, H3K4me3 enrichment).

Main Results:

• Identified 690 ZGA-associated genes in mice, including 119 novel genes.
• Defined S-ZGA genes, activated at ZGA and sustained throughout development.
• Found S-ZGA genes are regulated by promoter accessibility and H3K4me3 enrichment.
• Observed strong enrichment of S-ZGA genes in tumorigenesis and metastatic processes.

Conclusions:

• The study presents a novel, knowledge-independent computational framework for ZGA gene and timing identification.
• Defines S-ZGA genes, linking early development to potential roles in cancer.
• Provides new perspectives on molecular mechanisms in development and cancer progression.