Cap Analysis of Gene Expression Clarifies Transcriptomic Divergence Within Monozygotic Twin Pairs

Area of Science:

• Genomics
• Epigenetics
• Twin Studies

Background:

• Phenotypic variation arises from complex gene-environment interactions influencing gene expression.
• The relative contributions of genetic versus environmental factors to gene expression variability are not fully understood.
• Monozygotic twins share identical genes and common environments, differing only in non-shared factors, making them ideal for dissecting these influences.

Purpose of the Study:

• To investigate the differential susceptibility of annotated genes and retrotransposons to non-shared environmental and stochastic factors.
• To understand the regulatory mechanisms underlying expression divergence within monozygotic twin pairs.
• To identify specific transcription factors involved in environmentally influenced gene expression.

Main Methods:

• Cap analysis of gene expression (CAGE) was performed on three pairs of monozygotic twins.
• Gene expression profiles were used to cluster individuals and analyze annotated genes and retrotransposons (HERVs, LINEs).
• Motif analysis was conducted on differentially expressed annotated genes.

Main Results:

• Gene expression clustering confirmed each twin pair formed a monophyletic clade, indicating similarity in annotated gene expression.
• Expression of retrotransposons, including HERVs and LINEs, diverged significantly between individuals within each twin pair.
• Motif analysis implicated specificity protein/Krüppel-like factor family transcription factors in the expression divergence of annotated genes.

Conclusions:

• Annotated genes and retrotransposons exhibit distinct regulatory patterns in response to environmental influences.
• Retrotransposon expression is more sensitive to non-shared environmental and stochastic factors compared to annotated genes.
• Non-shared factors play a crucial role in shaping the epigenetic landscape and phenotypic variation, particularly through retrotransposon regulation.