title: The D355V mutation decreases EGR2 binding to an element within the Cx32 promoter.
abstract: 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.
authors.affiliation: Department of Neurological Sciences and Vision, University of Genova, Viale Benedetto XV, 6-16132 Genova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Musso
authors.forename: P
authors.initials: P
authors.lastname: Balestra
authors.forename: E
authors.initials: E
authors.lastname: Bellone
authors.forename: D
authors.initials: D
authors.lastname: Cassandrini
authors.forename: E
authors.initials: E
authors.lastname: Di Maria
authors.forename: L L
authors.initials: LL
authors.lastname: Doria
authors.forename: M
authors.initials: M
authors.lastname: Grandis
authors.forename: G L
authors.initials: GL
authors.lastname: Mancardi
authors.forename: A
authors.initials: A
authors.lastname: Schenone
authors.forename: G
authors.initials: G
authors.lastname: Levi
authors.forename: F
authors.initials: F
authors.lastname: Ajmar
authors.forename: P
authors.initials: P
authors.lastname: Mandich
mesh_terms: D000293:Adolescent; D001667:Binding, Competitive / Q000502:physiology; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000378:metabolism; D002648:Child; D017630:Connexins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051767:Early Growth Response Protein 2; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D009186:Myelin Sheath / Q000502:physiology; D017354:Point Mutation; D011401:Promoter Regions, Genetic / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; D014157:Transcription Factors; D000097002:Gap Junction beta-1 Protein; C497326:EGR2 protein, human