Premium
Control of myelination in Schwann cells: a Krox20 cis ‐regulatory element integrates Oct6, Brn2 and Sox10 activities
Author(s) -
Ghislain Julien,
Charnay Patrick
Publication year - 2006
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400573
Subject(s) - sox10 , enhancer , transcription factor , biology , zinc finger transcription factor , transcription (linguistics) , myelin , repressor , microbiology and biotechnology , genetics , zinc finger , gene , neuroscience , central nervous system , linguistics , philosophy
Myelination in Schwann cells is governed by several transcription factors, including the POU proteins Oct6 and Brn2, the high mobility group protein Sox10 and the zinc‐finger protein Krox20. How the function of these factors is integrated in the control of myelination has not been established. Previously, we identified an enhancer element controlling Krox20 expression throughout myelination in Schwann cells. In this paper, cell culture experiments were combined with transgenesis to identify transcription factors acting directly upstream of Krox20 . The results show that during the promyelin–myelin transition, Krox20 expression is directly activated by Oct6 and Brn2 acting on this enhancer. In addition, the enhancer‐dependent synergism between these POU proteins and Sox10 suggests that Krox20 expression requires this combination of factors. These results resolve previous controversy concerning the mechanism of action of Oct6 and Brn2 during myelination and provide an explanation for myelin deficiencies in Waardenberg–Hirschsprung disease patients whereby Sox10 mutations could lead to a loss of Krox20 expression.