Using epigenetics to identify transcription factors implicated in coordinating the critical period for song learning in juvenile male zebra finches

While it has long been observed that zebra finches (Taeniopygia guttata) have a critical period for song learning between post-hatch day 30 and post-hatch day 65, it remains an open question as to the underlying neural machinery that coordinates the onset as well as the offset of this learning period. Epigenetic mechanisms of regulation are now thought to play a key role in the transcriptional plasticity of key song-learning structures in the brain and can begin to account for the learning potential of a zebra finch during this period of its development. For example, the addition of an acetyl group to the lysine residue at position 27 on histone H3 as a result of exposure to song was postulated to affect the relationship between the histones and the genomic DNA and alter the probability that one or more transcription factors could bind to their corresponding binding sites. The total sum of these altered probabilities is what then could be a key driver of establishing the critical period for song learning in juvenile male zebra finches. ChIPseq analysis performed here confirmed this hypothesis, identifying a number of transcription factor binding sites differentially expressed in the finches that were exposed to song versus those that were not. Specifically, we identified the binding sites for transcription factors Zic1, Zic2, and MEIS3 which all have known functions in nervous system organization and proliferation, as well as HES6 and Hic1 which modulate neurogenesis and cell growth. Taken together, these results help to confirm the robust role that the acetylation of H3K27 has in mediating the accessibility of transcription factor binding sites and warrants further investigation into its putative role in the onset and offset of the critical period for song learning in zebra finches.