DNA Methylation Regulates Transcription Factor-Specific Neurodevelopmental but Not Sexually Dimorphic Gene Expression...

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Song learning in zebra finches is a complex learned behavior.
• The molecular mechanisms underlying song learning are not fully understood.

Purpose of the Study:

• To characterize transcriptomic and epigenomic changes during zebra finch telencephalon development.
• To investigate the roles of DNA methylation and dosage compensation in gene expression and sexual dimorphism during song learning.

Main Methods:

• RNA-sequencing for transcriptomic analysis.
• Reduced representation bisulfite sequencing (RRBS) and immunofluorescence for epigenomic analysis.
• Analysis of zebra finch telencephalon samples from 1 day post hatching to adulthood.

Main Results:

• Extensive age-dependent transcriptional changes were observed in the developing telencephalon.
• DNA methylation levels were low but increased with age, particularly in song control nuclei.
• Differential DNA methylation explained only a small part of gene expression changes, but was associated with transcription factors involved in neurodevelopment.
• Incomplete dosage compensation, not DNA methylation, was the primary driver of sexually dimorphic gene expression.

Conclusions:

• DNA methylation regulates neurodevelopmental gene expression by influencing transcription factor activity.
• Sexually dimorphic gene expression in the zebra finch telencephalon is largely explained by incomplete dosage compensation, which increases with age.