In silico analyses and global transcriptional profiling reveal novel putative targets for Pea3 transcription factor related to its function in neurons

• Published in: PloS one 2017-02, Vol.12 (2), p.e0170585-e0170585
• Main Authors: Kandemir, Başak, Dag, Ugur, Bakir Gungor, Burcu, Durasi, İlknur Melis, Erdogan, Burcu, Sahin, Eray, Sezerman, Ugur, Aksan Kurnaz, Isil
• Format: Article
• Language: English
• Subjects: Axon guidance; Binding sites; Biology and life sciences; Breast cancer; Bronchi; Bronchus; Cancer; Cell adhesion; Cell adhesion & migration; Cell adhesion molecules; Cell cycle; Cell Differentiation - genetics; Cell Differentiation - physiology; Cell Line, Tumor; Chromatin Immunoprecipitation; Combinatorial analysis; Computational neuroscience; DNA microarrays; Endocytosis - genetics; Endocytosis - physiology; Enzymes; Ephrin receptors; Ephrins; ETS protein; Genes; Growth factors; Humans; Immune system; Kidneys; Kinases; Mammals; Metastases; Metastasis; Molecular biology; Morphogenesis; Nervous system; Neuroblastoma; Neuroblastoma cells; Neuroblasts; Neurons; Neurons - cytology; Neurons - metabolism; Promoters; Promoters (Genetics); Prostate cancer; Proteins; Real-Time Polymerase Chain Reaction; Receptors; Research and Analysis Methods; Reverse Transcriptase Polymerase Chain Reaction; Semaphorins; Target recognition; Tissues; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0170585

Pea3 transcription factor belongs to the PEA3 subfamily within the ETS domain transcription factor superfamily, and has been largely studied in relation to its role in breast cancer metastasis. Nonetheless, Pea3 plays a role not only in breast tumor, but also in other tissues with branching morphogenesis, including kidneys, blood vasculature, bronchi and the developing nervous system. Identification of Pea3 target promoters in these systems are important for a thorough understanding of how Pea3 functions. Present study particularly focuses on the identification of novel neuronal targets of Pea3 in a combinatorial approach, through curation, computational analysis and microarray studies in a neuronal model system, SH-SY5Y neuroblastoma cells. We not only show that quite a number of genes in cancer, immune system and cell cycle pathways, among many others, are either up- or down-regulated by Pea3, but also identify novel targets including ephrins and ephrin receptors, semaphorins, cell adhesion molecules, as well as metalloproteases such as kallikreins, to be among potential target promoters in neuronal systems. Our overall results indicate that rather than early stages of neurite extension and axonal guidance, Pea3 is more involved in target identification and synaptic maturation.