SOX10 regulates expression of the SH3-domain kinase binding protein 1 (Sh3kbp1) locus in Schwann cells via an alternative promoter

被引:13
|
作者
Hodonsky, Chani J. [1 ]
Kleinbrink, Erica L. [1 ]
Charney, Kira N. [1 ]
Prasad, Megana [2 ]
Bessling, Seneca L. [2 ]
Jones, Erin A. [3 ]
Srinivasan, Rajini [4 ]
Svaren, John [4 ,5 ]
McCallion, Andrew S. [2 ]
Antonellis, Anthony [1 ,6 ]
机构
[1] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI USA
[2] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, McKusick Nathans Inst Genet Med, Baltimore, MD USA
[3] Univ Wisconsin, Program Cellular & Mol Biol, Madison, WI USA
[4] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA
[5] Univ Wisconsin, Dept Comparat Biosci, Madison, WI 53705 USA
[6] Univ Michigan, Sch Med, Dept Neurol, Ann Arbor, MI USA
关键词
SOX10; Schwann cells; Comparative sequence analysis; Transcriptional regulation; SH3KBP1; CIN85; TRANSCRIPTION FACTOR SOX10; GENE-EXPRESSION; ADAPTER PROTEIN; MYELINATION; EGR2; ZERO; MUTATIONS; ISOFORMS; LINES; RUK;
D O I
10.1016/j.mcn.2011.10.004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:85 / 96
页数:12
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