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Microphthalmia-associated transcription factor (MITF) acts as a master regulator of melanocyte development, function and survival by modulating various differentiation and cell-cycle progression genes. It has been demonstrated that MITF is an amplified oncogene in a fraction of human melanomas and that it also has an oncogenic role in human clear cell(More)
Systematic analyses of cancer genomes promise to unveil patterns of genetic alterations linked to the genesis and spread of human cancers. High-density single-nucleotide polymorphism (SNP) arrays enable detailed and genome-wide identification of both loss-of-heterozygosity events and copy-number alterations in cancer. Here, by integrating SNP array-based(More)
Genome-wide copy number analyses of human cancers identified a frequent 5p13 amplification in several solid tumour types, including lung (56%), ovarian (38%), breast (32%), prostate (37%) and melanoma (32%). Here, using integrative analysis of a genomic profile of the region, we identify a Golgi protein, GOLPH3, as a candidate targeted for amplification.(More)
Hair graying is the most obvious sign of aging in humans, yet its mechanism is largely unknown. Here, we used melanocyte-tagged transgenic mice and aging human hair follicles to demonstrate that hair graying is caused by defective self-maintenance of melanocyte stem cells. This process is accelerated dramatically with Bcl2 deficiency, which causes selective(More)
Our understanding of how chromatin structure influences cellular processes such as transcription and replication has been limited by a lack of nucleosome-positioning data in human cells. We describe a high-resolution microarray approach combined with an analysis algorithm to examine nucleosome positioning in 3,692 promoters within seven human cell lines.(More)
Microphthalmia (Mi) is a bHLHZip transcription factor that is essential for melanocyte development and postnatal function. It is thought to regulate both differentiated features of melanocytes such as pigmentation as well as proliferation/survival, based on phenotypes of mutant mouse alleles. Mi activity is controlled by at least two signaling pathways.(More)
Activating mutations in BRAF are the most common genetic alterations in melanoma. Inhibition of BRAF by small molecules leads to cell-cycle arrest and apoptosis. We show here that BRAF inhibition also induces an oxidative phosphorylation gene program, mitochondrial biogenesis, and the increased expression of the mitochondrial master regulator, PGC1α. We(More)
Although microRNAs (miRNAs) are key regulators of gene expression in normal human physiology and disease, transcriptional regulation of miRNAs is poorly understood, because most miRNA promoters have not yet been characterized. We identified the proximal promoters of 175 human miRNAs by combining nucleosome mapping with chromatin signatures for promoters. We(More)