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Evidence for a functional interaction of WNT10A and EBF1 in male-pattern baldness
- Source :
- PLoS ONE, Vol 16, Iss 9, p e0256846 (2021), PLoS ONE
- Publication Year :
- 2021
- Publisher :
- Public Library of Science (PLoS), 2021.
-
Abstract
- More than 300 genetic risk loci have been identified for male pattern baldness (MPB) but little is known about the exact molecular mechanisms through which the associated variants exert their effects on MPB pathophysiology. Here, we aimed at further elucidating the regulatory architecture of the MPB risk locus on chromosome (chr.) 2q35, where we have previously reported a regulatory effect of the MPB lead variant on the expression of WNT10A. A HaploReg database research for regulatory annotations revealed that the association signal at 2q35 maps to a binding site for the transcription factor EBF1, whose gene is located at a second MPB risk locus on chr. 5q33.3. To investigate a potential interaction between EBF1 and WNT10A during MPB development, we performed in vitro luciferase reporter assays as well as expression analyses and immunofluorescence co-stainings in microdissected human hair follicles. Our experiments confirm that EBF1 activates the WNT10A promoter and that the WNT10A/EBF1 interaction is impacted by the allelic expression of the MPB risk allele at 2q35. Expression analyses across different hair cycle phases and immunhistochemical (co)stainings against WNT10A and EBF1 suggest a predominant relevance of EBF1/WNT10A interaction for hair shaft formation during anagen. Based on these findings we suggest a functional mechanism at the 2q35 risk locus for MPB, where an MPB-risk allele associated reduction in WNT10A promoter activation via EBF1 results in a decrease in WNT10A expression that eventually results in anagen shortening, that is frequently observed in MPB affected hair follicles. To our knowledge, this study is the first follow-up study on MPB that proves functional interaction between two MPB risk loci and sheds light on the underlying pathophysiological mechanism at these loci.
- Subjects :
- Male
Hair Growth
Physiology
Epidemiology
Gene Expression
Biochemistry
Hair cycle
Gene expression
Medicine and Health Sciences
Promoter Regions, Genetic
Skin
Genetics
Multidisciplinary
Luciferase Assay
Enzymes
Bioassays and Physiological Analysis
Medicine
Male-pattern baldness
Anatomy
Integumentary System
Oxidoreductases
Luciferase
Research Article
Science
Locus (genetics)
Biology
Research and Analysis Methods
Hair Follicles
medicine
Humans
Allele
Transcription factor
Gene
Enzyme Assays
Anagen Phase
Biology and Life Sciences
Proteins
Chromosome
Alopecia
medicine.disease
Wnt Proteins
Gene Expression Regulation
Genetic Loci
Medical Risk Factors
Enzymology
Trans-Activators
Physiological Processes
Biochemical Analysis
Hair
Follow-Up Studies
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- PLOS ONE
- Accession number :
- edsair.doi.dedup.....a3911124da31408c85d8dbd88be55f35