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ChI(r)P-seq: FoxP2 Binding Sites Uncover Molecular Mechanisms Influencing Songbird Vocalizations

  • Author(s): Kimball, Todd Haswell
  • Advisor(s): White, Stephanie A
  • et al.
Abstract

The zebra finch, like humans, share a vocal learning phenotype and are an ideal model system to understand the molecular underpinnings of this multigenomic trait. Gene expression profiles examined in zebra finch have painted a dynamic picture of the complex genetic interplay required to enable vocal learning. The transcription factor FoxP2 is a key contributor to the gene regulation necessary for vocal learning in both humans and zebra finch. Examining the genes FoxP2 targets may provide the first step in possible pathways necessary for vocal learning. Chromatin immunoprecipitation (ChIP) captures DNA-protein interactions, and by using this approach, we were able to demonstrate FoxP2 binding sites within the genome. ChIP-qPCR provided validation of our approach and evidence of FoxP2 binding to the promoter of MAPK11, identified through our gene expression profile. Furthering this approach, ChIP-seq identified differential FoxP2 binding sites associated with developmental timepoints and sex differences, most notably Activating Transcription Factor 4 (ATF4), shown to influence synaptic plasticity and memory. The identification of FoxP2 binding sites and subsequent gene regulation will provide the starting point of pathways necessary for complex vocal development.

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