دورية أكاديمية
أعرض في EDS

Bromodomain and extra-terminal domain (BET) proteins regulate melanocyte differentiation.

التفاصيل البيبلوغرافية
العنوان: Bromodomain and extra-terminal domain (BET) proteins regulate melanocyte differentiation.
المؤلفون: Trivedi A; Department of Cancer Biology, University of Toledo College of Medicine and Life Sciences, 3035 Arlington Ave, Toledo, OH, 43614, USA., Mehrotra A; Department of Cancer Biology, University of Toledo College of Medicine and Life Sciences, 3035 Arlington Ave, Toledo, OH, 43614, USA.; Department of Genome Sciences, University of Washington School of Medicine, 1959 NE Pacific St, Seattle, WA, 98195, USA., Baum CE; Department of Pathology, University of Toledo College of Medicine and Life Sciences, 3035 Arlington Ave, Toledo, OH, 43614, USA., Lewis B; Department of Cancer Biology, University of Toledo College of Medicine and Life Sciences, 3035 Arlington Ave, Toledo, OH, 43614, USA., Basuroy T; Department of Cancer Biology, University of Toledo College of Medicine and Life Sciences, 3035 Arlington Ave, Toledo, OH, 43614, USA.; Cancer Center Division, Massachusetts General Hospital Harvard Medical School, 149 Thirteenth Street, 7th Floor, Charlestown, MA, 02129, USA., Blomquist T; Department of Pathology, University of Toledo College of Medicine and Life Sciences, 3035 Arlington Ave, Toledo, OH, 43614, USA., Trumbly R; Department of Cancer Biology, University of Toledo College of Medicine and Life Sciences, 3035 Arlington Ave, Toledo, OH, 43614, USA., Filipp FV; Cancer Systems Biology, Institute of Computational Biology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, München, 85764, Germany.; School of Life Sciences Weihenstephan, Technical University München, Maximus-von-Imhof-Forum 3, Freising, 85354, Germany., Setaluri V; Department of Dermatology, University of Wisconsin-Madison, The School of Medicine and Public Health, 1 S. Park Street, Madison, WI, 53715, USA., de la Serna IL; Department of Cancer Biology, University of Toledo College of Medicine and Life Sciences, 3035 Arlington Ave, Toledo, OH, 43614, USA. ivana.delaserna@utoledo.edu.
المصدر: Epigenetics & chromatin [Epigenetics Chromatin] 2020 Mar 10; Vol. 13 (1), pp. 14. Date of Electronic Publication: 2020 Mar 10.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101471619 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-8935 (Electronic) Linking ISSN: 17568935 NLM ISO Abbreviation: Epigenetics Chromatin Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : BioMed Central
مواضيع طبية MeSH: Cell Differentiation*, Cell Cycle Proteins/*metabolism , Melanocytes/*metabolism , Transcription Factors/*metabolism, Cell Cycle Proteins/genetics ; Cells, Cultured ; HEK293 Cells ; Humans ; Melanins/biosynthesis ; Melanins/genetics ; Melanocytes/cytology ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/metabolism ; Microphthalmia-Associated Transcription Factor/metabolism ; Monophenol Monooxygenase/genetics ; Monophenol Monooxygenase/metabolism ; Oxidoreductases/genetics ; Oxidoreductases/metabolism ; Promoter Regions, Genetic ; Protein Binding ; Transcription Factors/genetics
مستخلص: Background: Pharmacologic 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.
Results: Here 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.
Conclusion: These 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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معلومات مُعتمدة: R00 CA154887 United States CA NCI NIH HHS; R01 AR059379 United States AR NIAMS NIH HHS; R01AR059379 United States AR NIAMS NIH HHS
فهرسة مساهمة: Keywords: BET; BRD4; Bromodomain and extra-terminal domain; ChIP-Seq; Epigenomics; JQ1; MITF; Melanocyte differentiation; Melanoma; Pigmentation; Systems biology; Transcriptional networks
المشرفين على المادة: 0 (BRD2 protein, human)
0 (BRD4 protein, human)
0 (Cell Cycle Proteins)
0 (MITF protein, human)
0 (Melanins)
0 (Membrane Glycoproteins)
0 (Microphthalmia-Associated Transcription Factor)
0 (Transcription Factors)
EC 1.- (Oxidoreductases)
EC 1.14.18.- (TYRP1 protein, human)
EC 1.14.18.1 (Monophenol Monooxygenase)
تواريخ الأحداث: Date Created: 20200311 Date Completed: 20210421 Latest Revision: 20240423
رمز التحديث: 20240423
مُعرف محوري في PubMed: PMC7063807
DOI: 10.1186/s13072-020-00333-z
PMID: 32151278
قاعدة البيانات: MEDLINE
الوصف
تدمد:1756-8935
DOI:10.1186/s13072-020-00333-z