ArticleEpigenetics & chromatin2020
Bromodomain and extra-terminal domain (BET) proteins regulate melanocyte differentiation.
Article in Epigenetics & chromatin, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 21 citations in OpenAlex.
- Current Management and Emerging Therapies for Pediatric Vitiligo: A Narrative Review.Paediatric drugs · 2026Review
- MITF Is an Essential and Functionally Multifaceted Transcription Factor in Cutaneous Melanoma.Cancers · 2026Review
- Molecular Pathogenesis of Vitiligo: Emerging Roles of Epigenetic Regulation.Biomolecules & therapeutics · 2026Review
- Canine melanomas: MiTF and p38 expression and its correlation with the presence of lymphocytic infiltrate, proliferation, and survival.Veterinary research communications · 2026Article
- SETD6 mediates selective interaction and genomic occupancy of BRD4 and MITF in melanoma cells.NAR cancer · 2025Article
- Global loss of promoter-enhancer connectivity and rebalancing of gene expression during early colorectal cancer carcinogenesis.Nature cancer · 2024Article
- BET activity plays an essential role in control of stem cell attributes in Xenopus.Development (Cambridge, England) · 2024Article
- Selection signatures of wool color in Gangba sheep revealed by genome-wide SNP discovery.BMC genomics · 2024Article
- Regulation of Cell Plasticity by Bromodomain and Extraterminal Domain (BET) Proteins: A New Perspective in Glioblastoma Therapy.International journal of molecular sciences · 2023Review
- Acute respiratory distress syndrome enhances tumor metastasis into lungs: Role of BRD4 in the tumor microenvironment.International immunopharmacology · 2023Article
- SWI/SNF complex, promising target in melanoma therapy: Snapshot view.Frontiers in medicine · 2023Review
- Epigenetic and pharmacological control of pigmentation via Bromodomain Protein 9 (BRD9).Pigment cell & melanoma research · 2023Article
- Zebrafish ParalogsJournal of developmental biology · 2021Article
- Interrogating Epigenome toward Personalized Approach in Cutaneous Melanoma.Journal of personalized medicine · 2021Review
- On the application of 3d metals for C-H activation toward bioactive compounds: The key step for the synthesis of silver bullets.Beilstein journal of organic chemistry · 2021Review
- Brd/BET Proteins Influence the Genome-Wide Localization of the Kaposi's Sarcoma-Associated Herpesvirus and Murine Gammaherpesvirus Major Latency Proteins.Frontiers in microbiology · 2020Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundPharmacologic inhibition of bromodomain and extra-terminal (BET) proteins is currently being explored as a new therapeutic approach in cancer. Some studies have also implicated BET proteins as regulators of cell identity and differentiation through their interactions with lineage-specific factors. However, the role of BET proteins has not yet been investigated in melanocyte differentiation. Melanocyte inducing transcription factor (MITF) is the master regulator of melanocyte differentiation, essential for pigmentation and melanocyte survival. In this study, we tested the hypothesis that BET proteins regulate melanocyte differentiation through interactions with MITF.
resultsHere we show that chemical inhibition of BET proteins prevents differentiation of unpigmented melanoblasts into pigmented melanocytes and results in de-pigmentation of differentiated melanocytes. BET inhibition also slowed cell growth, without causing cell death, increasing the number of cells in G1. Transcriptional profiling revealed that BET inhibition resulted in decreased expression of pigment-specific genes, including many MITF targets. The expression of pigment-specific genes was also down-regulated in melanoma cells, but to a lesser extent. We found that RNAi depletion of the BET family members, bromodomain-containing protein 4 (BRD4) and bromodomain-containing protein 2 (BRD2) inhibited expression of two melanin synthesis enzymes, TYR and TYRP1. Both BRD4 and BRD2 were detected on melanocyte promoters surrounding MITF-binding sites, were associated with open chromatin structure, and promoted MITF binding to these sites. Furthermore, BRD4 and BRD2 physically interacted with MITF.
conclusionThese findings indicate a requirement for BET proteins in the regulation of pigmentation and melanocyte differentiation. We identified changes in pigmentation specific gene expression that occur upon BET inhibition in melanoblasts, melanocytes, and melanoma cells.
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