{"doi":"10.1111/pcmr.12611","title":"Beyond <scp>MITF</scp>: Multiple transcription factors directly regulate the cellular phenotype in melanocytes and melanoma","abstract":"<jats:title>Summary</jats:title><jats:p><jats:styled-content style=\"fixed-case\">MITF</jats:styled-content> governs multiple steps in the development of melanocytes, including specification from neural crest, growth, survival, and terminal differentiation. In addition, the level of <jats:styled-content style=\"fixed-case\">MITF</jats:styled-content> activity determines the phenotype adopted by melanoma cells, whether invasive, proliferative, or differentiated. However, <jats:styled-content style=\"fixed-case\">MITF</jats:styled-content> does not act alone. Here, we review literature on the transcription factors that co‐regulate <jats:styled-content style=\"fixed-case\">MITF</jats:styled-content>‐dependent genes. Ch<jats:styled-content style=\"fixed-case\">IP</jats:styled-content>‐seq studies have indicated that the transcription factors <jats:styled-content style=\"fixed-case\">SOX</jats:styled-content>10, <jats:styled-content style=\"fixed-case\">YY</jats:styled-content>1, and <jats:styled-content style=\"fixed-case\">TFAP</jats:styled-content>2A co‐occupy subsets of regulatory elements bound by <jats:styled-content style=\"fixed-case\">MITF</jats:styled-content> in melanocytes. Analyses at single loci also support roles for <jats:styled-content style=\"fixed-case\">LEF</jats:styled-content>1, <jats:styled-content style=\"fixed-case\">RB</jats:styled-content>1, <jats:styled-content style=\"fixed-case\">IRF</jats:styled-content>4, and <jats:styled-content style=\"fixed-case\">PAX</jats:styled-content>3 acting in combination with <jats:styled-content style=\"fixed-case\">MITF</jats:styled-content>, while sequence motif analyses suggest that additional transcription factors colocalize with <jats:styled-content style=\"fixed-case\">MITF</jats:styled-content> at many melanocyte‐specific regulatory elements. However, the precise biochemical functions of each of these <jats:styled-content style=\"fixed-case\">MITF</jats:styled-content> collaborators and their contributions to gene expression remain to be elucidated. Analogous to the transcriptional networks in morphogen‐patterned tissues during embryogenesis, we anticipate that the level of <jats:styled-content style=\"fixed-case\">MITF</jats:styled-content> activity is controlled not only by the concentration of activated <jats:styled-content style=\"fixed-case\">MITF</jats:styled-content>, but also by additional transcription factors that either quantitatively or qualitatively influence the expression of <jats:styled-content style=\"fixed-case\">MITF</jats:styled-content>‐target genes.</jats:p>","journal":"Pigment Cell &amp; Melanoma Research","year":2017,"id":607070,"datarank":0.7077748306942643,"base_score":4.718498871295094,"endowment":4.718498871295094,"self_citation_contribution":0.7077748306942643,"citation_network_contribution":0.0,"self_endowment_contribution":0.7077748306942643,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":111,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":582472,"name":"Eric Van Otterloo","orcid":"0000-0001-5958-5742","position":1,"is_corresponding":false},{"id":457318,"name":"Robert A. Cornell","orcid":"0000-0003-4207-9100","position":2,"is_corresponding":false},{"id":1558668,"name":"Hannah E. Seberg","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Beyond <scp>MITF</scp>: Multiple transcription factors directly regulate the cellular phenotype in melanocytes and melanoma","abstract":"<jats:title>Summary</jats:title><jats:p><jats:styled-content style=\"fixed-case\">MITF</jats:styled-content> governs multiple steps in the development of melanocytes, including specification from neural crest, growth, survival, and terminal differentiation. In addition, the level of <jats:styled-content style=\"fixed-case\">MITF</jats:styled-content> activity determines the phenotype adopted by melanoma cells, whether invasive, proliferative, or differentiated. However, <jats:styled-content style=\"fixed-case\">MITF</jats:styled-content> does not act alone. Here, we review literature on the transcription factors that co‐regulate <jats:styled-content style=\"fixed-case\">MITF</jats:styled-content>‐dependent genes. Ch<jats:styled-content style=\"fixed-case\">IP</jats:styled-content>‐seq studies have indicated that the transcription factors <jats:styled-content style=\"fixed-case\">SOX</jats:styled-content>10, <jats:styled-content style=\"fixed-case\">YY</jats:styled-content>1, and <jats:styled-content style=\"fixed-case\">TFAP</jats:styled-content>2A co‐occupy subsets of regulatory elements bound by <jats:styled-content style=\"fixed-case\">MITF</jats:styled-content> in melanocytes. Analyses at single loci also support roles for <jats:styled-content style=\"fixed-case\">LEF</jats:styled-content>1, <jats:styled-content style=\"fixed-case\">RB</jats:styled-content>1, <jats:styled-content style=\"fixed-case\">IRF</jats:styled-content>4, and <jats:styled-content style=\"fixed-case\">PAX</jats:styled-content>3 acting in combination with <jats:styled-content style=\"fixed-case\">MITF</jats:styled-content>, while sequence motif analyses suggest that additional transcription factors colocalize with <jats:styled-content style=\"fixed-case\">MITF</jats:styled-content> at many melanocyte‐specific regulatory elements. However, the precise biochemical functions of each of these <jats:styled-content style=\"fixed-case\">MITF</jats:styled-content> collaborators and their contributions to gene expression remain to be elucidated. Analogous to the transcriptional networks in morphogen‐patterned tissues during embryogenesis, we anticipate that the level of <jats:styled-content style=\"fixed-case\">MITF</jats:styled-content> activity is controlled not only by the concentration of activated <jats:styled-content style=\"fixed-case\">MITF</jats:styled-content>, but also by additional transcription factors that either quantitatively or qualitatively influence the expression of <jats:styled-content style=\"fixed-case\">MITF</jats:styled-content>‐target genes.</jats:p>","is_dataset_classified":null,"base_score":4.718498871295094,"endowment":4.718498871295094,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28649789","pmcid":null,"openalex_id":"https://openalex.org/W2713351076","authors":[],"funders":[{"funder_name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","grant_id":"R01 AR062547","title":null},{"funder_name":"National Science Foundation","grant_id":"IOS‐114722","title":null}],"total_grants":2,"fwci":4.1797,"citation_percentile":0.95220102,"influential_citations":0,"citation_trend":[{"year":2018,"count":8},{"year":2019,"count":15},{"year":2020,"count":13},{"year":2021,"count":11},{"year":2022,"count":17},{"year":2023,"count":12},{"year":2024,"count":14},{"year":2025,"count":16},{"year":2026,"count":5}],"oa_status":"bronze","license":"http://onlinelibrary.wiley.com/termsAndConditions#am","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/pcmr.12611","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/pcmr.12611","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fpcmr.12611","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/pcmr.12611","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1111/pcmr.12611","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/am-pdf/10.1111/pcmr.12611","host_type":"publisher"},{"url":"https://doi.org/10.1111/pcmr.12611","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28649789","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC5939569","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5939569","host_type":"repository"}],"fields_of_study":["melanin and skin pigmentation","Skin Protection and Aging","Silk-based biomaterials and applications"],"mesh_terms":["Animals","Humans","Melanocytes","Melanoma","Models, Biological","Phenotype","Transcription Factors","Microphthalmia-Associated Transcription Factor"],"keywords":["Microphthalmia-associated transcription factor","Phenotype","Transcription factor","Melanoma","Cell biology","Biology","Genetics","Gene"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T05:42:55.833979Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}