In silico analyses and global transcriptional profiling reveal novel putative targets for Pea3 transcription factor related to its function in neurons.
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.
Gebze Technical University, Department of Molecular Biology and Genetics, Kocaeli, Turkey.|Yeditepe University, Biotechnology Graduate Program, Kayisdagi, Istanbul, Turkey.
Başak
B
Kandemir
Yeditepe University, Biotechnology Graduate Program, Kayisdagi, Istanbul, Turkey.
Ugur
U
Dag
Sabanci University, Faculty of Engineering and Natural Sciences, Istanbul, Turkey.
Burcu
B
Bakir Gungor
Gebze Technical University, Department of Molecular Biology and Genetics, Kocaeli, Turkey.|Sabanci University, Faculty of Engineering and Natural Sciences, Istanbul, Turkey.
İlknur Melis
İM
Durasi
Yeditepe University, Biotechnology Graduate Program, Kayisdagi, Istanbul, Turkey.
Burcu
B
Erdogan
Gebze Technical University, Department of Molecular Biology and Genetics, Kocaeli, Turkey.|Yeditepe University, Biotechnology Graduate Program, Kayisdagi, Istanbul, Turkey.
Eray
E
Sahin
Sabanci University, Faculty of Engineering and Natural Sciences, Istanbul, Turkey.
Ugur
U
Sezerman
Gebze Technical University, Department of Molecular Biology and Genetics, Kocaeli, Turkey.|Gebze Technical University, Institute of Biotechnology, Kocaeli, Turkey.
Isil
http://orcid.org/0000-0002-5587-4763
I
Aksan Kurnaz
D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004705:Endocytosis / Q000235:genetics / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D014157:Transcription Factors; C065788:transcription factor PEA3