Mutations in the early growth response 2 (EGR2) gene are associated with some forms of Charcot--Marie--Tooth disease (CMT) and other demyelinating neuropathies. These mutations modify the EGR2 binding to specific DNA sequences suggesting a role in the transcriptional control of myelination-specific genes. Here we show that the D355V mutation, associated with a CMT case combining axonal and demyelinating abnormalities, reduces three times the affinity of EGR2 to its consensus sequence and ten times its affinity to a sequence in the human Cx32 promoter. These findings could indicate that this EGR2 mutation leads to the development of CMT1 through the transcriptional deregulation of Cx32 gene.
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| http://dx.doi.org/10.1006/nbdi.2001.0397 | DOI Listing |
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Different consequences of EGR2 mutants on the transactivation of human Cx32 promoter.
Neurobiol Dis
February 2003
Department of Neurosciences, Ophthalmology, and Genetics, University of Genoa, c/o DIMI Viale Benedetto XV, 6-16132 Genova, Italy.
The early growth response 2 (EGR2) transcription factor plays a crucial role in peripheral nerve myelination. Mutations of this gene are associated with a wide variety of demyelinating neuropathies differing from each other in the severity of nerve injury. Although the expression of EGR2 mutants inhibits the transactivation of myelin gene promoters, the exact molecular mechanism by which these mutations cause the alteration of the myelination process is still unknown.
View Article and Find Full Text PDFThe D355V mutation decreases EGR2 binding to an element within the Cx32 promoter.
Neurobiol Dis
August 2001
Department of Neurological Sciences and Vision, University of Genova, Viale Benedetto XV, 6-16132 Genova, Italy.
Mutations in the early growth response 2 (EGR2) gene are associated with some forms of Charcot--Marie--Tooth disease (CMT) and other demyelinating neuropathies. These mutations modify the EGR2 binding to specific DNA sequences suggesting a role in the transcriptional control of myelination-specific genes. Here we show that the D355V mutation, associated with a CMT case combining axonal and demyelinating abnormalities, reduces three times the affinity of EGR2 to its consensus sequence and ten times its affinity to a sequence in the human Cx32 promoter.
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