Characterization of the Promoter Region of the Human Melanocortin-1 Receptor (MC1R) Gene

Moro, Osamu; Ideta, Ritsuro; Ifuku, Ohji

doi:10.1006/bbrc.1999.1228

Cited by 46 publications

(40 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They found that the promoter haplotypes with a combination of À490T, À445A and À226T, 98.5% of which bore the 163Q allele in the coding region, showed lower OR for initiating freckles and solar lentigines than did the human consensus haplotype ( À490C, À445G, À226A). They suggested that the À490C4T variant might be responsible for the decreased promoter activity, based on the finding by Moro et al 69 that a deletion from À517 to À447 damages the promoter activity. Therefore, impaired function in the promoter region, caused by the variant(s) in linkage disequilibrium with R163Q, may explain the association between the 163Q allele and the lightness of skin, which we found in this study.…”

Section: Discussionmentioning

confidence: 99%

Association of melanocortin 1 receptor gene (MC1R) polymorphisms with skin reflectance and freckles in Japanese

et al. 2012

View full text Add to dashboard Cite

Most studies on the genetic basis of human skin pigmentation have focused on people of European ancestry and only a few studies have focused on Asian populations. We investigated the association of skin reflectance and freckling with genetic variants of melanocortin 1 receptor (MC1R) gene in Japanese. DNA samples were obtained from a total of 653 Japanese individuals (ages 19-40 years) residing in Okinawa; skin reflectance was measured using a spectrophotometer and freckling status was determined for each individual. Lightness index (L*) and freckling status were not correlated with age, body mass index or ancestry (Ryukyuan or Main Islanders of Japan). Among the 10 nonsynonymous variants that were identified by direct sequencing of the coding region of MC1R, two variants-R163Q and V92M-with the derived allele frequencies of 78.6 and 5.5%, respectively, were most common. Multiple regression analysis showed that the 163Q allele and the presence of nonsynonymous rare variants (allele frequencies o5%) were significantly associated with an increase in sex-standardized skin lightness (L* of CIELAB (CIE 1976 (L*a*b*) color space)) of the inner upper arm. Relative to the 92V allele, the 92M allele was significantly associated with increased odds of freckling. This is the first study to show an association between the 163Q allele and skin reflectance values; this association indicated that light-toned skin may have been subjected to positive selection in East Asian people.

show abstract

Section: Discussionmentioning

confidence: 99%

Association of melanocortin 1 receptor gene (MC1R) polymorphisms with skin reflectance and freckles in Japanese

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Some of the important MC1R cis-regulatory sequences and transcription factors that interact with the MC1R promoter have been identified in mice and humans (Moro et al 1999). Detection and identification of substitutions affecting MC1R regulation is challenging, but developing in vitro assays to assess the effects of specific substitutions on MC1R expression is tractable.…”

Section: ; Figure 2)mentioning

confidence: 99%

A window on the genetics of evolution:MC1Rand plumage colouration in birds

2005

View full text Add to dashboard Cite

Melanins are a ubiquitous component of plumage colouration in birds and serve a wide variety of functions. Although the genetic control of melanism has been studied in chickens and other domestic species, little was known about the molecular genetics of melanin distribution in wild birds until recently. Studies have now revealed that a single locus, the melanocortin-1 receptor (MC1R) locus, is responsible for melanic polymorphisms in at least three unrelated species: the bananaquit, the snow goose and the arctic skua. Results show that melanism was a derived trait and allow other evolutionary inferences about the history of melanism to be made. The role of MC1R in plumage patterning is surprisingly diverse among different species. The conserved molecular basis for the evolution of melanism in birds and several other vertebrates is probably related to low pleiotropic effects at the MC1R.

show abstract

“…The MC4-R belongs to a family of five melanocortin receptors. Promoter analyses have been mostly performed on two of the encoding genes, hMC1-R (Moro et al 1999), mMC2-R and hMC2-R (Naville et al 1994, Cammas et al 1997, Shimizu et al 1997) and these genes lack both TATA and CAAT boxes.…”

Section: Discussionmentioning

confidence: 99%

Expression of the human melanocortin-4 receptor gene is controlled by several members of the Sp transcription factor family

Blondet¹,

Gout²,

Durand³

et al. 2005

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

The melanocortin-4 receptor (MC4-R) plays a key role in the hypothalamic control of food intake, lending importance to the understanding of the mechanisms that regulate its expression. To identify factors controlling the expression of the human (h) MC4-R gene, a fragment containing 1253 bp of the 58-flanking region of the hMC4-R gene was isolated. A series of hMC4-R luciferase constructs were developed and used to transiently transfect HEK293 and GT1-7 cell lines, both expressing endogenous MC4-R mRNA. Deletion analysis of the 1253 bp fragment showed that the basal promoter activity is mainly restricted to the 179 bp upstream of the transcription start site in both cell types. Mutation of a putative Sp1-binding site located at position −76 bp resulted in a dramatic reduction of the luciferase activity in HEK293 and GT1-7 cells by 87 and 80% respectively. Both in vitro and in vivo studies (gel shift and chromatin immunoprecipitation analyses) revealed binding of both Sp1 and Sp3 to this site in HEK293 cells. Cotransfection with an Sp1 expression vector in Drosophila cells that do not express Sp1, in conjunction with treatment of HEK293 cells with mithramycin A, a specific inhibitor of Sp1, confirmed the role of Sp1. For the first time, we have demonstrated that the constitutive activity of the hMC4-R promoter is dependent upon Sp transcription factors.

show abstract

Characterization of the Promoter Region of the Human Melanocortin-1 Receptor (MC1R) Gene

Cited by 46 publications

References 46 publications

Association of melanocortin 1 receptor gene (MC1R) polymorphisms with skin reflectance and freckles in Japanese

Association of melanocortin 1 receptor gene (MC1R) polymorphisms with skin reflectance and freckles in Japanese

A window on the genetics of evolution:MC1Rand plumage colouration in birds

Expression of the human melanocortin-4 receptor gene is controlled by several members of the Sp transcription factor family

Contact Info

Product

Resources

About