Sequence divergence and retrotransposon insertion underlie interspecific epigenetic differences in primates.

Area of Science:

• Comparative genomics
• Epigenetics
• Developmental biology

Background:

• High human-chimpanzee genome similarity suggests epigenomic changes drive phenotypic divergence.
• Epigenetic modifications, like histone methylation, play a crucial role in gene regulation without altering DNA sequence.

Purpose of the Study:

• To investigate epigenomic and transcriptomic differences between human and chimpanzee induced pluripotent stem cells (iPSCs).
• To identify the role of histone modifications and retrotransposons in species-specific gene expression and phenotypic divergence.

Main Methods:

• Generation and analysis of transcriptome and epigenome data (H3K4me3, H3K27me3) from human and chimpanzee iPSCs.
• Identification of species-specific histone modification regions and associated genomic features, including transcription factor binding motifs and retrotransposons.
• Comparison of epigenetic states with species-biased enhancers in cranial neural crest cells.

Main Results:

• High similarity in overall transcriptome and H3K4me3/H3K27me3 patterns between human and chimpanzee iPSCs.
• Species-specific H3K4me3 regions enriched for pluripotency transcription factor binding motifs (POU5F1, SOX2).
• Species-specific retrotransposon insertions (LTR5_Hs in humans, LTR5_Pt in chimpanzees) created H3K4me3 regions linked to increased gene expression.
• Human iPSCs exhibit more species-specific H3K27me3 regions and bivalent domains.
• Limited overlap between species-specific epigenetic marks in iPSCs and species-biased enhancers in cranial neural crest cells.

Conclusions:

• Induced pluripotent stem cells are valuable models for studying evolutionary epigenome dynamics.
• Epigenomic differences, influenced by transcription factor binding and retrotransposons, contribute significantly to human-chimpanzee phenotypic divergence.
• Epigenetic differences in developmental enhancers emerge later in development, distinct from early iPSC differences.