A distal Schwann cell-specific enhancer mediates axonal regulation of the Oct-6 transcription factor during peripheral nerve development and regeneration.
The POU domain transcription factor Oct-6 is a major regulator of Schwann cell differentiation and myelination. During nerve development and regeneration, expression of Oct-6 is under the control of axonal signals. Identification of the cis-acting elements necessary for Oct-6 gene regulation is an important step in deciphering the complex signalling between Schwann cells and axons governing myelination. Here we show that a fragment distal to the Oct-6 gene, containing two DNase I-hypersensitive sites, acts as the Oct-6 Schwann cell-specific enhancer (SCE). The SCE is sufficient to drive spatially and temporally correct expression, during both normal peripheral nerve development and regeneration. We further demonstrate that a tagged version of Oct-6, driven by the SCE, rescues the peripheral nerve phenotype of Oct-6-deficient mice. Thus, our isolation and characterization of the Oct-6 SCE provides the first description of a cis-acting genetic element that responds to converging signalling pathways to drive myelination in the peripheral nervous system.
|Keywords||*Enhancer Elements (Genetics), Animals, Axons/metabolism, Base Sequence, Cell Communication, Cell Differentiation, Conserved Sequence, Cyclic AMP/pharmacology, Gene Expression Regulation, Developmental, HSP70 Heat-Shock Proteins/genetics, Humans, Mice, Mice, Mutant Strains, Mutagenesis, Myelin Sheath/*metabolism, Nerve Regeneration/*physiology, Neurons/cytology/*metabolism, Octamer Transcription Factor-6, Peripheral Nerves/*embryology, Research Support, Non-U.S. Gov't, Schwann Cells/cytology/drug effects/*metabolism, Sequence Deletion, Transcription Factors/*genetics|
|Persistent URL||dx.doi.org/10.1093/emboj/19.12.2992, hdl.handle.net/1765/12878|
Mandemakers, W.J., Zwart, R., Jaegle, M.M., Walbeehm, E.T., Visser, P., Grosveld, F.G., & Meijer, D.. (2000). A distal Schwann cell-specific enhancer mediates axonal regulation of the Oct-6 transcription factor during peripheral nerve development and regeneration.. EMBO Journal, 2992–3003. doi:10.1093/emboj/19.12.2992