SOX10 regulates expression of the SH3-domain kinase binding protein 1 (Sh3kbp1) locus in Schwann cells via an alternative promoter.
The transcription factor SOX10 has essential roles in neural crest-derived cell populations, including myelinating Schwann cells-specialized glial cells responsible for ensheathing axons in the peripheral nervous system. Importantly, SOX10 directly regulates the expression of genes essential for proper myelin function. To date, only a handful of SOX10 target loci have been characterized in Schwann cells. Addressing this lack of knowledge will provide a better understanding of Schwann cell biology and candidate loci for relevant diseases such as demyelinating peripheral neuropathies. We have identified a highly-conserved SOX10 binding site within an alternative promoter at the SH3-domain kinase binding protein 1 (Sh3kbp1) locus. The genomic segment identified at Sh3kbp1 binds to SOX10 and displays strong promoter activity in Schwann cells in vitro and in vivo. Mutation of the SOX10 binding site ablates promoter activity, and ectopic expression of SOX10 in SOX10-negative cells promotes the expression of endogenous Sh3kbp1. Combined, these data reveal Sh3kbp1 as a novel target of SOX10 and raise important questions regarding the function of SH3KBP1 isoforms in Schwann cells.
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, USA.
Chani J
CJ
Hodonsky
Erica L
EL
Kleinbrink
Kira N
KN
Charney
Megana
M
Prasad
Seneca L
SL
Bessling
Erin A
EA
Jones
Rajini
R
Srinivasan
John
J
Svaren
Andrew S
AS
McCallion
Anthony
A
Antonellis
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D005786:Gene Expression Regulation; D056426:Genetic Loci; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051381:Rats; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012583:Schwann Cells / Q000378:metabolism*; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C433810:SH3KBP1 protein, human; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; C498782:Sh3kbp1 protein, mouse; C411889:Sh3kbp1 protein, rat; C527924:Sox10 protein, mouse; C527925:Sox10 protein, rat; D029961:Zebrafish Proteins; C442229:sox10 protein, zebrafish