التفاصيل البيبلوغرافية
| العنوان: |
A Polymorphism in IRF4 Affects Human Pigmentation through a Tyrosinase-Dependent MITF/TFAP2A Pathway |
| المؤلفون: |
Richard A. Sturm, Kristin Bergsteinsdottir, Pravin J. Mishra, Robert A. Cornell, Glenn Merlino, Lionel Larue, David E. Fisher, Christian Praetorius, Agnar Helgason, Ulduz Sobhiafshar, David U. Gorkin, Paul S. Meltzer, Eric Van Otterloo, Margret H. Ogmundsdottir, Valérie Petit, Andrew S. McCallion, Martin I. Sigurdsson, Eiríkur Steingrímsson, Aaron G. Smith, Simon N. Stacey, Kathleen C. Robinson, N. C. Tolga Emre, Theresa Guo, Alexander M. Metcalf, Erna Magnúsdóttir, M. Raza Zaidi, Kari Stefansson, Sean Davis, Stacie K. Loftus, David R. Adams, Christine Grill, Reuben S.Q. Kim, William J. Pavan |
| المصدر: |
ResearcherID |
| بيانات النشر: |
Elsevier BV, 2013. |
| سنة النشر: |
2013 |
| مصطلحات موضوعية: |
Tyrosinase, Molecular Sequence Data, Melanocyte, Biology, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, TFAP2A, Mice, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Humans, Enhancer, Transcription factor, Zebrafish, 030304 developmental biology, Genetics, 0303 health sciences, Base Sequence, integumentary system, Pigmentation, Biochemistry, Genetics and Molecular Biology(all), Microphthalmia-associated transcription factor, Enhancer Elements, Genetic, medicine.anatomical_structure, Transcription Factor AP-2, 030220 oncology & carcinogenesis, Interferon Regulatory Factors, Melanocytes, Signal Transduction, IRF4, Interferon regulatory factors |
| الوصف: |
Sequence polymorphisms linked to human diseases and phenotypes in genome-wide association studies often affect non-coding regions. A single nucleotide polymorphism (SNP) within an intron of the gene encoding Interferon Regulatory Factor 4 (IRF4), a transcription factor with no known role in melanocyte biology, is strongly associated with sensitivity of skin to sun exposure, freckles, blue eyes and brown hair color. Here we demonstrate that this SNP lies within an enhancer of IRF4 transcription in melanocytes. The allele associated with this pigmentation phenotype impairs binding of the TFAP2A transcription factor which together with the melanocyte master regulator MITF, regulates activity of the enhancer. Assays in zebrafish and mice reveal that IRF4 cooperates with MITF to activate expression of Tyrosinase (TYR), an essential enzyme in melanin synthesis. Our findings provide a clear example of a non-coding polymorphism that affects a phenotype by modulating a developmental gene regulatory network. |
| تدمد: |
0092-8674 |
| DOI: |
10.1016/j.cell.2013.10.022 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b6d46366b6efffd1951b1e2a93bfc46d |
| Rights: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....b6d46366b6efffd1951b1e2a93bfc46d |
| قاعدة البيانات: |
OpenAIRE |