Locus-wide identification of Egr2/Krox20 regulatory targets in myelin genes.
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.
Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
Sung-Wook
SW
Jang
Rajini
R
Srinivasan
Erin A
EA
Jones
Guannan
G
Sun
Sunduz
S
Keles
Courtney
C
Krueger
Li-Wei
LW
Chang
Rakesh
R
Nagarajan
John
J
Svaren
D000818:Animals; D000831:Animals, Newborn; D045744:Cell Line, Tumor; D051767:Early Growth Response Protein 2 / Q000235:genetics / Q000378:metabolism*; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D018390:Gene Targeting / Q000379:methods*; D056426:Genetic Loci / Q000235:genetics*; D008546:Melanoma, Experimental / Q000235:genetics; D051379:Mice; D009186:Myelin Sheath / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000502:physiology
D051767:Early Growth Response Protein 2; D051638:Ether-A-Go-Go Potassium Channels; C109500:Kcnh6 protein, rat