MTF1 binds to metal-responsive element e within the ATP7B promoter and is a strong candidate in regulating the ATP7B expression.
Carcinoma, Hepatocellular
/ genetics
Copper-Transporting ATPases
/ genetics
DNA-Binding Proteins
/ genetics
Gene Expression Regulation, Neoplastic
Hep G2 Cells
Humans
Liver Neoplasms
/ genetics
Metals
/ metabolism
Promoter Regions, Genetic
Response Elements
Transcription Factors
/ genetics
Transcription Factor MTF-1
Wilson's disease
metal regulatory transcription factor 1 (MTF1)
metal-responsive element (MRE)
Journal
Annals of human genetics
ISSN: 1469-1809
Titre abrégé: Ann Hum Genet
Pays: England
ID NLM: 0416661
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
20
12
2018
revised:
02
09
2019
accepted:
05
09
2019
pubmed:
10
10
2019
medline:
5
2
2021
entrez:
10
10
2019
Statut:
ppublish
Résumé
Wilson's disease is an autosomal recessive disorder resulting from copper excess. Some patients with clinical Wilson's disease symptoms exhibit no or only heterozygous pathogenic variants in the coding region of the disease-causing ATP7B gene. Therefore, the ATP7B promoter region is of special interest. Metal-responsive elements (MREs) located in the ATP7B promoter are promising motifs in modulating the ATP7B expression. We studied protein interaction of MREe, MREc, and MREd by electrophoretic mobility shift assays and revealed specific interactions for all MREs. We further narrowed down the specific binding site. Proteins potentially binding to the three MREs were identified by MatInspector analyses. Metal regulatory transcription factor 1 (MTF1) could be validated to bind to MREe by electrophoretic mobility shift assays. ATP7B promoter-driven reporter gene expression was significantly increased because of this interaction. MTF1 is a strong candidate in regulating the ATP7B expression through MREe binding.
Substances chimiques
DNA-Binding Proteins
0
Metals
0
Transcription Factors
0
ATP7B protein, human
EC 7.2.2.8
Copper-Transporting ATPases
EC 7.2.2.8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
195-200Informations de copyright
© 2019 The Authors. Annals of Human Genetics published by University College London (UCL) and John Wiley & Sons Ltd.
Références
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