Diddens Jolien, Coussement Louis, Frankl-Vilches Carolina, Majumdar Gaurav, Steyaert Sandra, Ter Haar Sita M, Galle Jeroen, De Meester Ellen, De Keulenaer Sarah, Van Criekinge Wim, Cornil Charlotte A, Balthazart Jacques, Van Der Linden Annemie, De Meyer Tim, Vanden Berghe Wim
Laboratory of Protein Chemistry, Proteomics and Epigenetic Signaling (PPES), Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Biobix: Laboratory of Bioinformatics and Computational Genomics, Department of Data Analysis and Mathematical Modeling, Ghent University, Ghent, Belgium.
Front Cell Dev Biol. 2021 Mar 19;9:583555. doi: 10.3389/fcell.2021.583555. eCollection 2021.
Song learning in zebra finches () is a prototypical example of a complex learned behavior, yet knowledge of the underlying molecular processes is limited. Therefore, we characterized transcriptomic (RNA-sequencing) and epigenomic (RRBS, reduced representation bisulfite sequencing; immunofluorescence) dynamics in matched zebra finch telencephalon samples of both sexes from 1 day post hatching (1 dph) to adulthood, spanning the critical period for song learning (20 and 65 dph). We identified extensive transcriptional neurodevelopmental changes during postnatal telencephalon development. DNA methylation was very low, yet increased over time, particularly in song control nuclei. Only a small fraction of the massive differential expression in the developing zebra finch telencephalon could be explained by differential CpG and CpH DNA methylation. However, a strong association between DNA methylation and age-dependent gene expression was found for various transcription factors (i.e., , , and ) involved in neurodevelopment. Incomplete dosage compensation, independent of DNA methylation, was found to be largely responsible for sexually dimorphic gene expression, with dosage compensation increasing throughout life. In conclusion, our results indicate that DNA methylation regulates neurodevelopmental gene expression dynamics through steering transcription factor activity, but does not explain sexually dimorphic gene expression patterns in zebra finch telencephalon.
斑胸草雀的鸣叫学习是复杂习得行为的典型例子，但对其潜在分子过程的了解有限。因此，我们对孵化后1天（1 dph）至成年期的雌雄斑胸草雀端脑匹配样本中的转录组（RNA测序）和表观基因组（RRBS，简化代表性亚硫酸氢盐测序；免疫荧光）动态进行了表征，涵盖鸣叫学习的关键时期（20和65 dph）。我们在出生后端脑发育过程中发现了广泛的转录性神经发育变化。DNA甲基化水平很低，但随时间增加，尤其是在鸣叫控制核中。在发育中的斑胸草雀端脑中，大量差异表达中只有一小部分可由CpG和CpH DNA甲基化差异来解释。然而，对于参与神经发育的各种转录因子（即 、 和 ），发现DNA甲基化与年龄依赖性基因表达之间存在强关联。发现不完全剂量补偿（独立于DNA甲基化）在很大程度上导致了性别二态性基因表达，且剂量补偿在整个生命过程中增加。总之，我们的结果表明，DNA甲基化通过调控转录因子活性来调节神经发育基因表达动态，但不能解释斑胸草雀端脑中的性别二态性基因表达模式。
