Locus-wide identification of Egr2/Krox20 regulatory targets in myelin genes.
J Neurochem
; 115(6): 1409-20, 2010 Dec.
Article
en En
| MEDLINE
| ID: mdl-21044070
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Marcación de Gen
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Canales de Potasio Éter-A-Go-Go
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Proteína 2 de la Respuesta de Crecimiento Precoz
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Sitios Genéticos
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Vaina de Mielina
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Neurochem
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos