Premium
Locus‐wide identification of Egr2/Krox20 regulatory targets in myelin genes
Author(s) -
Jang SungWook,
Srinivasan Rajini,
Jones Erin A,
Sun Guannan,
Keles Sunduz,
Krueger Courtney,
Chang LiWei,
Nagarajan Rakesh,
Svaren John
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.07045.x
Subject(s) - chromatin immunoprecipitation , myelin , biology , sox10 , schwann cell , chromatin , gene , transcription factor , microbiology and biotechnology , microarray analysis techniques , gene knockdown , locus (genetics) , enhancer , genetics , gene expression , promoter , neuroscience , central nervous system
J. Neurochem. (2010) 115, 1409–1420. Abstract Myelination of peripheral nerves by Schwann cells depends upon a gene regulatory network controlled by early growth response Egr2/Krox20, which is specifically required for Schwann cells to initiate and maintain myelination. To elucidate the mechanism by which Egr2 regulates gene expression during myelination, we have performed chromatin immunoprecipitation analysis on myelinating rat sciatic nerve in vivo . The resulting samples were applied to a tiled microarray consisting of a broad spectrum of genes that are activated or repressed in Egr2‐deficient mice. The results show extensive binding within myelin‐associated genes, as well as some genes that become repressed in myelinating Schwann cells. Many of the Egr2 peaks coincide with regions of open chromatin, which is a marker of enhancer regions. In addition, further analysis showed that there is substantial colocalization of Egr2 binding with Sox10, a transcription factor required for Schwann cell specification and other stages of Schwann cell development. Finally, we have found that Egr2 binds to promoters of several lipid biosynthetic genes, which is consistent with their dramatic up‐regulation during the formation of lipid‐rich myelin. Overall, this analysis provides a locus‐wide profile of Egr2 binding patterns in major myelin‐associated genes using myelinating peripheral nerve.