Involvement of<i>mi</i>-Transcription Factor in Expression of α-Melanocyte-Stimulating Hormone Receptor in Cultured Mast Cells of Mice

Adachi, Shiro; Morii, Eiichi; Kim, Dae-ki; Ogihara, Hideki; Jippo, Tomoko; Ito, Akihiko; Lee, Young-Mi; Kitamura, Yukihiko

doi:10.4049/jimmunol.164.2.855

Cited by 51 publications

(48 citation statements)

References 40 publications

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“…Consistent with previous work showing that Mitf activates and binds to a promoter region containing a potential Mitf binding site (58,59), Mitf was also associated with the endogenous Mc-1r promoter, and activation of the Mc-1r gene correlated with hyperacetylation of histone H4. Thus, Mitf may recruit histone acetyltransferases but not SWI/SNF enzymes to the Mc-1r promoter.…”

Section: Mitf Promotes Recruitment Of Swi/snf Enzymes To and Histone supporting

confidence: 77%

“…It binds to the melanocortin-1 receptor (Mc-1r), a member of a subfamily of G protein-coupled receptors that is expressed in melanocytes and other cells (82). Mitf has been shown to activate the Mc-1r promoter in both melanocytes and mast cells (58,59); therefore, we tested whether Mitf could activate Mc-1r expression in fibroblasts and whether its expression required SWI/SNF enzymes. We found that Mc-1r was expressed in fibroblasts at low levels and was activated by Mitf in an SWI/SNF-independent manner.…”

Section: Discussionmentioning

confidence: 99%

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The Microphthalmia-associated Transcription Factor Requires SWI/SNF Enzymes to Activate Melanocyte-specific Genes

Serna

Ohkawa

Higashi

et al. 2006

Journal of Biological Chemistry

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The microphthalmia transcription factor (Mitf ) activates melanocyte-specific gene expression, is critical for survival and proliferation of melanocytes during development, and has been described as an oncogene in malignant melanoma. SWI/SNF complexes are ATP-dependent chromatin-remodeling enzymes that play a role in many developmental processes. To determine the requirement for SWI/SNF enzymes in melanocyte differentiation, we introduced Mitf into fibroblasts that inducibly express dominant negative versions of the SWI/SNF ATPases, Brahma or Brahma-related gene 1 (BRG1). These dominant negative SWI/SNF components have been shown to inhibit gene activation events that normally require SWI/SNF enzymes. We found that Mitf-mediated activation of a subset of endogenous melanocyte-specific genes required SWI/SNF enzymes but that cell-cycle regulation occurred independently of SWI/SNF function. Activation of tyrosinase-related protein 1, a melanocytespecific gene, correlated with SWI/SNF-dependent changes in chromatin accessibility at the endogenous locus. Both BRG1 and Mitf could be localized to the tyrosinase-related protein 1 and tyrosinase promoters by chromatin immunoprecipitation, whereas immunofluorescence and immunoprecipitation experiments indicate that Mitf and BRG1 co-localized in the nucleus and physically interacted. Together these results suggest that Mitf can recruit SWI/SNF enzymes to melanocyte-specific promoters for the activation of gene expression via induced changes in chromatin structure at endogenous loci.Melanocytes are pigment-producing cells that are developmentally derived from the neural crest and that comprise 1-2% of the epidermis (1). They are also present on the epithelial surfaces of mucous membranes, hair follicles, the cochlea of the inner ear, and both the uvea and conjunctiva of the eye (2, 3). On the skin, they play a photoprotective role by synthesizing and distributing melanin (4). Excessive exposure to UV radiation has been linked to the transformation of cutaneous melanocytes to melanoma, a cancer that has steadily increased in frequency and is difficult to treat (5, 6).Microphthalmia-associated transcription factor (Mitf ) 2 is the "master regulator" of melanocyte differentiation and was elegantly shown to convert fibroblasts into dendritic cells that express melanocyte-specific genes (7). It is important for the commitment, proliferation, and survival of melanocytes during neural crest cell migration, and null mutations of the mouse Mitf gene result in complete absence of melanocytes and lack of pigmentation in the skin, eyes, and inner ear (8, 9). Two human diseases resulting from mutations in the MITF gene are Waardenburg type 2 syndrome and Tietz syndrome, both of which are characterized by pigmentary disturbances and sensineural deafness (8).Mitf is a basic helix-loop-helix leucine zipper transcription factor that binds DNA either as a homodimer or as a heterodimer with TFE3, TFEB, or TFEC to conserved E boxes (CAC(G/A)TG) in the promoters of its target genes, which incl...

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Section: Mitf Promotes Recruitment Of Swi/snf Enzymes To and Histone supporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

The Microphthalmia-associated Transcription Factor Requires SWI/SNF Enzymes to Activate Melanocyte-specific Genes

Serna

Ohkawa

Higashi

et al. 2006

Journal of Biological Chemistry

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“…Pigmentation-associated transcriptional targets of MITF include the pigment enzyme genes tyrosinase, TRP1, TRP2/Dct, which were recognized to contain an evolutionarily conserved consensus promoter/enhancer element that matches the MITF recognition sequence (Bentley et al 1994;Hemesath et al 1994;Yasumoto et al 1994). Additional differentiation-associated genes include Pmel17/silver/gp100 (which encodes the melanoma diagnostic epitope HMB45) (Halaban et al 1996;Baxter and Pavan 2003;Du et al 2003), MelanA/Mart1 , Melastatin (TRPM1) (Miller et al 2004;Zhiqi et al 2004), AIM1 (ocular albinism 4 gene) (Du and Fisher 2002), Ocular albinism 1 gene (OA1) (Vetrini et al 2004), VMD2 (Esumi et al 2004), HIF1␣ (Busca et al 2005), Plasminogen activator inhibitor-1 (Murakami et al 2006), numerous mast cell targets of MITF including Prostaglandin D2, multiple mast cell genes including proteases, various adhesion molecules and others (see Ito et al 2004;Morii et al 2004;Takeda et al 2006 and references therein), and melanocortin 1 receptor (MC1R) in mast cells and possibly in melanocytes (Adachi et al 2000;Smith et al 2001;Aoki and Moro 2002). Numerous additional genes are being identified through expression microarrays, and are liable to reflect the multiple steps involved between signaling, expressing, packaging, and exporting pigment.…”

Section: Transcriptional Targets Of Mitfmentioning

confidence: 99%

Malignant melanoma: genetics and therapeutics in the genomic era

2006

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Cell for cell, probably no human cancer is as aggressive as melanoma. It is among a handful of cancers whose dimensions are reported in millimeters. Tumor thickness approaching 4 mm presents a high risk of metastasis, and a diagnosis of metastatic melanoma carries with it an abysmal median survival of 6-9 mo. What features of this malignancy account for such aggressive behavior? Is it the migratory history of its cell of origin or the programmed adaptation of its differentiated progeny to environmental stress, particularly ultraviolet radiation? While the answers to these questions are far from complete, major strides have been made in our understanding of the cellular, molecular, and genetic underpinnings of melanoma. More importantly, these discoveries carry profound implications for the development of therapies focused directly at the molecular engines driving melanoma, suggesting that we may have reached the brink of an unprecedented opportunity to translate basic science into clinical advances. In this review, we attempt to summarize our current understanding of the genetics and biology of this disease, drawing from expanding genomic information and lessons from development and genetically engineered mouse models. In addition, we look forward toward how these new insights will impact on therapeutic options for metastatic melanoma in the near future. The diseaseMelanomas most often arise within epidermal melanocytes of the skin, although they can also derive from noncutaneous melanocytes such as those lining the choroidal layer of the eye, GI and GU mucosal surfaces, or the meninges. Melanoma is also among the more common causes of "metastatic cancer of unknown primary," which may reflect either a propensity to arise in unexpected sites along the neural crest migratory route, or rapid growth of poorly differentiated lesions arising from indolent or unrecognized cutaneous primary lesions. Clinical staging for primary cutaneous melanoma employs measurements of thickness (in millimeters), presence of ulceration, penetration through cutaneous layers, mitotic rate, evidence of "in transit" metastasis, tumor spread to draining lymph nodes, and evidence of distant metastasis. Management issues in melanoma can be classified in terms of prevention, diagnosis, local disease management, and treatment of metastatic disease.In view of the epidemiological and emerging experimental evidence linking melanoma incidence to UV exposure and skin phototype, prevention and screening strategies represent key areas for reduction of disease incidence and severity. For most cutaneous melanomas in the so-called radial growth phase (e.g., thin melanomas), surgical removal affords curative treatment. In contrast, a significant fraction of patients diagnosed with intermediate-thickness (2-4 mm) cutaneous melanoma eventually succumb to recurrence at regional or distant sites.Critical biological questions facing the melanoma research community include: (1) What genetic and environmental factors contribute to and/or modulate risk of melanom...

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“…21 E-box is present immediately upstream of the transcriptional initiation site. 28,29) The presence of an E-box suggests the possibility that MITF regulates Mc1r gene expression by the same transcriptional mechanism as Tyr and Trp1. 28) Thus MITF appears to play a central role in the expression of the enzymes and receptors essential to melanogenesis.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effect of Elephantopus mollis H.B. and K. Extract on Melanogenesis in B16 Murine Melanoma Cells by Downregulating Microphthalmia-Associated Transcription Factor Expression

Hasegawa

Furuya

Mizuno

et al. 2010

Bioscience, Biotechnology, and Biochemistry

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In this study, the inhibitory effect of Elephantopus mollis H.B. and K. extract on melanogenesis in B16 murine melanoma cells was examined and possible mechanisms were elucidated. The melanin content in B16 cells decreased when they were treated with E. mollis extract. Inhibition was accompanied by reduced expression of tyrosinase (TYR) and tyrosinaserelated protein 1 (TRP1). Furthermore, the expression level of microphthalmia-associated transcription factor (MITF), a major transcriptional regulator of genes encoding melanogenic enzymes such as Tyr and Trp1, decreased as assessed by western blotting and quantitative reverse transcriptase polymerase chain reaction (RT-PCR). These results suggest that E. mollis extract reduces melanogenesis by downregulating Mitf expression, leading to reduced expression of Tyr and Trp1. In addition, melanocortin-1 receptor (MC1R) expression was downregulated by E. mollis extract, suggesting desensitization to -melanocyte-stimulating hormone ( -MSH) of cells treated with the extract.

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Involvement ofmi-Transcription Factor in Expression of α-Melanocyte-Stimulating Hormone Receptor in Cultured Mast Cells of Mice

Cited by 51 publications

References 40 publications

The Microphthalmia-associated Transcription Factor Requires SWI/SNF Enzymes to Activate Melanocyte-specific Genes

The Microphthalmia-associated Transcription Factor Requires SWI/SNF Enzymes to Activate Melanocyte-specific Genes

Malignant melanoma: genetics and therapeutics in the genomic era

Inhibitory Effect of Elephantopus mollis H.B. and K. Extract on Melanogenesis in B16 Murine Melanoma Cells by Downregulating Microphthalmia-Associated Transcription Factor Expression

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