Different consequences of EGR2 mutants on the transactivation of human Cx32 promoter

Marco Musso; Piercesare Balestra; Franco Taroni; Emilia Bellone; Paola Mandich

doi:10.1016/s0969-9961(02)00018-9

Different consequences of EGR2 mutants on the transactivation of human Cx32 promoter

Neurobiol Dis. 2003 Feb;12(1):89-95. doi: 10.1016/s0969-9961(02)00018-9.

Authors

Marco Musso¹, Piercesare Balestra, Franco Taroni, Emilia Bellone, Paola Mandich

Affiliation

¹ Department of Neurosciences, Ophthalmology, and Genetics, University of Genoa, c/o DIMI Viale Benedetto XV, 6-16132 Genova, Italy. genetica.medica@unige.it

PMID: 12609493
DOI: 10.1016/s0969-9961(02)00018-9

Abstract

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. Recently, it was reported that EGR2 is directly involved in the transcriptional regulation of Connexin 32, a myelin gene frequently mutated in peripheral neuropathies. Here we describe the differential effect of two EGR2 mutants; while mutant D355V partially induces Cx32 promoter, mutant R381H does not. Furthermore, we show that a sequence located at -216, recognized by the wild-type and the mutant D355V recombinant proteins, is relevant for promoter transactivation.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Base Sequence / genetics
Binding Sites / genetics
Charcot-Marie-Tooth Disease / genetics
Charcot-Marie-Tooth Disease / metabolism
Connexins / genetics*
Connexins / metabolism
DNA / analysis
DNA / genetics
DNA Footprinting
DNA-Binding Proteins / deficiency*
DNA-Binding Proteins / genetics
Demyelinating Diseases / genetics*
Demyelinating Diseases / metabolism
Demyelinating Diseases / physiopathology
Early Growth Response Protein 2
Gap Junction beta-1 Protein
Genes, Regulator / genetics
HeLa Cells
Humans
Mutation / genetics*
Myelin Sheath / genetics*
Myelin Sheath / metabolism
Myelin Sheath / pathology
Peripheral Nerves / metabolism*
Peripheral Nerves / pathology
Peripheral Nerves / physiopathology
Phenotype
Promoter Regions, Genetic / genetics
Protein Isoforms / genetics
Recombinant Fusion Proteins / genetics
Transcription Factors / deficiency*
Transcription Factors / genetics
Transcriptional Activation / genetics
Zinc Fingers / genetics

Substances

Connexins
DNA-Binding Proteins
EGR2 protein, human
Early Growth Response Protein 2
Protein Isoforms
Recombinant Fusion Proteins
Transcription Factors
DNA