Sox proteins in melanocyte development and melanoma

Harris, Melissa L.; Baxter, Laura L.; Loftus, Stacie K.; Pavan, William J.

doi:10.1111/j.1755-148x.2010.00711.x

Cited by 148 publications

(139 citation statements)

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“…Second, these putative melanocyte enhancers are enriched for sequence motifs predicted to bind key melanocyte TFs, including SOX10 and MITF, as detected by DREME ( Fig. 2C Harris et al 2010). Third, analysis with GREAT (McLean et al 2010) reveals that genes proximal to the putative melanocyte enhancers (within ;50 kb; see GREAT methods) are significantly associated with Gene Ontology (GO) terms relevant to melanocyte biology, including melanoma, melanosome, pigmentation, and melanocyte differentiation (Table 1).…”

Section: Resultsmentioning

confidence: 94%

Integration of ChIP-seq and machine learning reveals enhancers and a predictive regulatory sequence vocabulary in melanocytes

et al. 2012

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We take a comprehensive approach to the study of regulatory control of gene expression in melanocytes that proceeds from large-scale enhancer discovery facilitated by ChIP-seq; to rigorous validation in silico, in vitro, and in vivo; and finally to the use of machine learning to elucidate a regulatory vocabulary with genome-wide predictive power. We identify 2489 putative melanocyte enhancer loci in the mouse genome by ChIP-seq for EP300 and H3K4me1. We demonstrate that these putative enhancers are evolutionarily constrained, enriched for sequence motifs predicted to bind key melanocyte transcription factors, located near genes relevant to melanocyte biology, and capable of driving reporter gene expression in melanocytes in culture (86%; 43/50) and in transgenic zebrafish (70%; 7/10). Next, using the sequences of these putative enhancers as a training set for a supervised machine learning algorithm, we develop a vocabulary of 6-mers predictive of melanocyte enhancer function. Lastly, we demonstrate that this vocabulary has genome-wide predictive power in both the mouse and human genomes. This study provides deep insight into the regulation of gene expression in melanocytes and demonstrates a powerful approach to the investigation of regulatory sequences that can be applied to other cell types.

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Section: Resultsmentioning

confidence: 94%

Integration of ChIP-seq and machine learning reveals enhancers and a predictive regulatory sequence vocabulary in melanocytes

et al. 2012

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“…Based on phylogenetic analysis of their HMG domains, SOX genes can be separated into subgroups A-J, A-H of which are represented in mouse and humans [17]. Because they are expressed in many tissues, it is not surprisingly that SOX genes are implicated in the etiology of many diseases and certain cancers.…”

Section: Discussionmentioning

confidence: 99%

SOXs in human prostate cancer: implication as progression and prognosis factors

et al. 2012

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BackgroundSOX genes play an important role in a number of developmental processes. Potential roles of SOXs have been demonstrated in various neoplastic tissues as tumor suppressors or promoters depending on tumor status and types. The aim of this study was to investigate the involvement of SOXs in the progression and prognosis of human prostate cancer (PCa).MethodsThe gene expression changes of SOXs in human PCa tissues compared with non-cancerous prostate tissues was detected using gene expression microarray, and confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohositochemistry. The roles of these genes in castration resistance were investigated in LNCaP xenograft model of PCa.ResultsThe microarray analysis identified three genes (SOX7, SOX9 and SOX10) of SOX family that were significantly dis-regulated in common among four PCa specimens. Consistent with the results of the microarray, differential mRNA and protein levels of three selected genes were found in PCa tissues by QRT-PCR analysis and immunohistochemistry. Additionally, we found that the immunohistochemical staining scores of SOX7 in PCa tissues with higher serum PSA level (P = 0.02) and metastasis (P = 0.03) were significantly lower than those with lower serum PSA level and without metastasis; the increased SOX9 protein expression was frequently found in PCa tissues with higher Gleason score (P = 0.02) and higher clinical stage (P < 0.0001); the down-regulation of SOX10 tend to be found in PCa tissues with higher serum PSA levels (P = 0.03) and advanced pathological stage (P = 0.01). Moreover, both univariate and multivariate analyses showed that the down-regulation of SOX7 and the up-regulation of SOX9 were independent predictors of shorter biochemical recurrence-free survival. Furthermore, we discovered that SOX7 was significantly down-regulated and SOX9 was significantly up-regulated during the progression to castration resistance.ConclusionsOur data offer the convince evidence that the dis-regulation of SOX7, SOX9 and SOX10 may be associated with the aggressive progression of PCa. SOX7 and SOX9 may be potential markers for prognosis in PCa patients. Interestingly, the down-regulation of SOX7 and the up-regulation of SOX9 may be important mechanisms for castration-resistant progression of PCa.

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“…Sox10 is a member of the SoxE family of transcription factors, which contain a high mobility group (HMG) box DNA-dependent dimerization domain (reviewed in Harris et al, 2010 (Potterf et al, 2001). The requirement of Sox10 for Mitf and Dct expression suggests a role for Sox10 in the initial specification of melanoblasts.…”

Section: Cell Intrinsic Factorsmentioning

confidence: 99%

“…has also been shown to regulate the transcription of genes required for melanin synthesis, including Dopachrome tautomerase (Dct), and Tyrosinase (Tyr) (reviewed in Harris et al, 2010).…”

Section: Sox10mentioning

confidence: 99%

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The Role of the Transcription Factor Ets1 in Melanocyte Development

Tavares¹

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Sox proteins in melanocyte development and melanoma

Cited by 148 publications

References 146 publications

Integration of ChIP-seq and machine learning reveals enhancers and a predictive regulatory sequence vocabulary in melanocytes

Integration of ChIP-seq and machine learning reveals enhancers and a predictive regulatory sequence vocabulary in melanocytes

SOXs in human prostate cancer: implication as progression and prognosis factors

The Role of the Transcription Factor Ets1 in Melanocyte Development

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