Synergistic transcriptional activation by Sox10 and Sp1 family members

• Published in: Neuropharmacology 2000-10, Vol.39 (13), p.2615-2623
• Main Authors: Melnikova, Irena N, Lin, Horng-Ru, Blanchette, Adam R, Gardner, Paul D
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cells, Cultured; Chimera - genetics; DNA-Binding Proteins - genetics; Fundamental and applied biological sciences. Psychology; High Mobility Group Proteins - genetics; Mice; Molecular and cellular biology; Molecular genetics; Neuronal nicotinic acetylcholine receptors; Plasmids; Precipitin Tests; Promoter Regions, Genetic - genetics; Protein Biosynthesis; Receptors, Nicotinic - genetics; Sox10; Sox10 protein; SOXE Transcription Factors; Sp1; Sp1 protein; Sp1 Transcription Factor - genetics; Sp3; Sp3 Transcription Factor; Transcription Factors - genetics; Transcription, Genetic - genetics; Transcription. Transcription factor. Splicing. Rna processing; Transcriptional synergy; Transfection
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/S0028-3908(00)00125-8

Neuronal nicotinic acetylcholine receptors (nAChR) are expressed at specific times during development and in discrete neuronal populations. Transcriptional regulation of the receptor genes clearly plays a key role in the molecular pathway underlying the expression of these critical synaptic components. In an effort to understand this regulation, we focus upon the genes encoding three receptor subunits: α3, α5 and β4. These subunits are genomically clustered and constitute the predominant nAChR subtype expressed in the peripheral nervous system. We and others demonstrated that the general transcription factors, Sp1 and Sp3, can transactivate the promoter of each subunit gene. Further, we showed that the regulatory factor Sox10 transactivates the α3 and β4 promoters and does so in a cell-type-specific manner. Interestingly, the Sp- and Sox10-binding sites on the β4 promoter are located immediately adjacent to each other, raising the possibility that the two sets of factors functionally interact to regulate receptor gene expression. Consistent with this hypothesis, we demonstrated that the proteins can directly interact. Here, we extend these observations and show that Sox10 and the Sp factors functionally interact, leading to synergistic transcriptional activation in a cholinergic cell line. Finally, evidence for the existence of cell-type-specific co-regulators for Sp1 and Sox10 is presented.