背景声乐学习是一种罕见的,融合的特征,是人类语言和鸟鸣的基础。叉头盒P2(FoxP2)转录因子似乎对于两种类型的学习信号都是必需的,因为人类FoxP2的突变会导致言语障碍,并破坏其在斑马雀中的表达会损害男性特定的歌曲学习。在幼年和成年雄性雀类中,在歌唱过程中,纹状体FoxP2mRNA和蛋白质在歌曲专用神经元内急剧下降,表明其转录靶标也是行为调控的。鸣鸟中这些目标的身份,以及它们是否因性别而异,发育和/或行为条件,基本上是未知的。结果在这里,我们使用染色质免疫沉淀,然后测序(ChIP-Seq)来鉴定男性和女性中FoxP2结合的基因组位点,少年和成人,唱歌和不唱歌的鸟。我们的结果表明,强大的FoxP2结合集中在基因的推定启动子区域。可能被FoxP2结合的基因数量因条件而异,建议与性别相关的候选人目标的专门角色,年龄,和行为状态。我们通过生物信息验证了这些结合靶标,与以前的研究和生物化学的比较,使用推定靶基因的抗体进行免疫组织化学。基因本体论分析显示,人类语言和语言相关功能仅在男性中丰富,与该物种中歌曲学习的性二态一致。相对于成年人,在青少年中发现的此类目标较少,这表明这个监管网络随着成熟而扩展。在歌唱条件下发现最少的与言语有关的目标,与有据可查的歌唱驱动的FoxP2在鸣禽纹状体中的下调一致。总体结论,这些数据提供了FoxP2在鸟类发声学习者中的监管格局的初始目录,为未来的研究提供几十个目标基因,并提供对声乐学习的分子基础的见解。
UNASSIGNED: Vocal learning is a rare, convergent trait that is fundamental to both human speech and birdsong. The Forkhead Box P2 (
FoxP2) transcription factor appears necessary for both types of learned signals, as human mutations in
FoxP2 result in speech deficits, and disrupting its expression in zebra finches impairs male-specific song learning. In juvenile and adult male finches, striatal
FoxP2 mRNA and protein decline acutely within song-dedicated neurons during singing, indicating that its transcriptional targets are also behaviorally regulated. The identities of these targets in songbirds, and whether they differ across sex, development and/or behavioral conditions, are largely unknown.
UNASSIGNED: Here we used chromatin immunoprecipitation followed by sequencing (ChIP-Seq) to identify genomic sites bound by FoxP2 in male and female, juvenile and adult, and singing and non-singing birds. Our results suggest robust
FoxP2 binding concentrated in putative promoter regions of genes. The number of genes likely to be bound by
FoxP2 varied across conditions, suggesting specialized roles of the candidate targets related to sex, age, and behavioral state. We validated these binding targets both bioinformatically, with comparisons to previous studies and biochemically, with immunohistochemistry using an antibody for a putative target gene. Gene ontology analyses revealed enrichment for human speech- and language-related functions in males only, consistent with the sexual dimorphism of song learning in this species. Fewer such targets were found in juveniles relative to adults, suggesting an expansion of this regulatory network with maturation. The fewest speech-related targets were found in the singing condition, consistent with the well-documented singing-driven down-regulation of FoxP2 in the songbird striatum.
UNASSIGNED: Overall, these data provide an initial catalog of the regulatory landscape of FoxP2 in an avian vocal learner, offering dozens of target genes for future study and providing insight into the molecular underpinnings of vocal learning.