Identification of the minimal melanocyte-specific promoter in the melanocortin receptor 1 gene

نویسندگان

  • Stefania Miccadei
  • Barbara Pascucci
  • Mauro Picardo
  • Pier Giorgio Natali
  • Donato Civitareale
چکیده

BACKGROUND The understanding of cutaneous pigmentation biology is relevant from the biologic and clinical point of view. The binding of alpha-melanocortin and its specific receptor, on the plasma membrane of melanin synthesising cells, plays a crucial role in melanins biosynthesis. Furthermore, loss of MC1R function is associated with an increased incidence of melanoma and non-melanoma skin cancer. The expression of the alpha-melanocortin receptor gene is highly controlled but, at the present, region responsible for tissue-specific activity of the gene promoter has not been identified. METHODS We have cloned the genomic sequences upstream the human MC1R coding gene. A DNA fragment of 5 kilobases upstream the human MC1R encoding sequence was placed in front of a reporter gene and several deletion mutants of such fragment have been prepared. These constructs have been tested for the ability to drive the melanocyte-specific gene expression of the reporter gene using transfection experiments in melanocyte and non-melanocyte cell lines. From these experiments we identified a DNA fragment with the ability to drive the gene transcription in a tissue-specific way and we used this small DNA fragment in DNA-protein interaction assays. RESULTS We show that the 150 base pairs upstream the MC1R gene initiation codon are able to drive the melanocyte-specific gene transcription. Furthermore, we provide experimental evidences suggesting that on such minimal melanocyte-specific gene promoter can assemble tissue-specific complexes. CONCLUSION The present results strongly imply that the transcriptional regulation of the melanocyte-specific MC1R gene requires an internal promoter located in the 150 base pairs upstream the initiation codon.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Polymorphisms in Melanocortin Receptor 1 Gene in Goat Breeds: A Window for Coat Color Controling Mechanism

The broad goal of this research was to examine the nature of the Melanocortin receptor 1 (MC1R) locus on the coat color phenotype of seven goat breeds with different color coat. Blood samples were collected from five Iranian indigenous (Khalkhal, Markhor, Naeini, Najdi and Tali) and two exotic (Cashmere and Saanen) goat breeds. Polymerase chain reaction restriction fragment length polymorphism ...

متن کامل

A 99mTc-tricine-HYNIC-labeled Peptide Targeting the Melanocortin-1 Receptor for Melanoma Imaging

Melanocortin-1 (MC1) receptor is an attractive melanoma-specific target for the development of α-MSH peptide based imaging and therapeutic agents. In this work a new lactam bridge α-MSH analogue was synthesized and radiolabeled with 99mTc via HYNIC chelator and tricine as co-ligand. Also, stability in human serum, receptor bound internalization and tissue biodistribution in tumor bearing nude m...

متن کامل

Hypermethylation of E-Cadherin and Estro-gen Receptor- Gene Promoter and Its Association with Clinicopathological Features of Breast Cancer in Iranian Patients

Background: Aberrant methylation of cytosine-guanine dinucleotide islands leads to inactivation of tumor suppressor genes in breast cancer. Tumor suppressor genes are unmethylated in normal tissue and often become hypermethylated during tumor formation, leading to gene silencing. We investigated the association between E-cadherin (CDH1) and estrogen receptor-α (ESRα) gene promoter methylation a...

متن کامل

Association of the melanocortin-3(MC3R) receptor gene with growth and reproductive traits in Mazandaran indigenous chicken

Melanocortin-3 receptor (MC3R) plays an important role in the central control of energy homeostasis, and several functional polymorphisms of this gene have been detected. We have studied MC3R as a candidate gene responsible for variation in economically important traits in chicken. To determine the association between MC3R polymorphism and phenotypic variation, a total of 190 individuals from b...

متن کامل

Promoter hypermethylation of KLOTHO; an anti-senescence related gene in colorectal cancer patients of Kashmir valley

Hypermethylation of CpG islands located in the promoter regions of genes is a major event in the development of the majority of cancer types, due to the subsequent aberrant silencing of important tumor suppressor genes. KLOTHO; a novel gene associated primarily with suppressing senescence has been shown to contribute to tumorigenesis as a result of its impaired function. Recently the relevance ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Journal of Experimental & Clinical Cancer Research : CR

دوره 27  شماره 

صفحات  -

تاریخ انتشار 2008