Análise in silico de potenciais alvos do fator de transcrição zenk em um modelo de aprendizado vocal

Abstract

Memory formation requires gene expression triggered by neuronal activity. This response includes a series of activity-dependent genes that are thought to mediate the changes necessary for memory consolidation and maintenance. Among these genes, zenk (also known as egr1) was one of the first examples of a behaviorally driven gene, and has since been linked to memory formation in rodents. Nonetheless, the role of this gene in vocal learning, the exact behavior in which zenk was first discovered as activity-dependent, remains elusive. Because zenk encodes a transcription factor that must exert its effects through the regulation of downstream targets, in the present work we sought to computationally identify its potential binding sites in the zebra finch genome (Taeniopygia guttata). For that, we used a motif scanning tool, called FIMO (Find Individual Motif Occurrences), to identify thousands of potential target sites in promoter regions. We next restricted the target gene list to genes regulated during singing in a region that is central to vocal learning and production, the HVC. Our results show that within this restricted list, ZENK binding sites were present in 64% of the genes, the highest enrichment among all 122 transcription factors analysed. In addition, we observed a significant superposition between the putative targets of ZENK and two other transcription factors, namely KLF4 and NR2C2, raising the possibility of previously unknown interactions between them. Altogether, our in silico results indicate that ZENK has the potential to be a key regulator in the transcriptional response in song control neurons. Importantly, these findings will guide future experiments to determine, and therefore validate, ZENK-targets in vivo.