Chromatin Accessibility Landscape in Human Early Embryos and Its Association with Evolution

Area of Science:

• Developmental Biology
• Epigenetics
• Genomics

Background:

• The chromatin regulatory landscape's role in early human embryogenesis is largely unexplored.
• Understanding gene regulation dynamics is crucial for developmental processes.

Purpose of the Study:

• To investigate the establishment of chromatin accessibility during human early embryogenesis.
• To explore the role of transcription factors like OCT4 in early development and zygotic genome activation (ZGA).
• To understand the relationship between gene age, promoter characteristics, and expression timing.

Main Methods:

• DNase I hypersensitive site (DHS) sequencing was employed to map chromatin accessibility.
• Analysis of OCT4 binding motifs and their enrichment.
• Correlation of gene age and promoter CpG content with DHS establishment and gene expression.

Main Results:

• Chromatin accessibility is gradually established throughout human early embryogenesis.
• OCT4 binding motifs are enriched at ZGA in humans, and OCT4 is crucial for human ZGA, unlike in mice.
• Younger genes and genes with lower CpG promoters are associated with later DHS establishment and expression, while older genes show earlier patterns.
• Active human transposons (SVA, HERV-K) harbor DHSs and are expressed in early embryos but not in differentiated tissues.

Conclusions:

• This study reveals the dynamic establishment of the chromatin landscape during human early development.
• OCT4's species-specific role in ZGA highlights evolutionary differences in developmental regulation.
• Gene age and transposon activity are significant factors in regulating gene and transposon expression during embryogenesis, offering an evolutionary developmental perspective.