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Basuroy, T.* ; Dreier, M.* ; Baum, C.* ; Blomquist, T.* ; Trumbly, R.* ; Filipp, F.V. ; de la Serna, I.L.*

Epigenetic and pharmacological control of pigmentation via Bromodomain Protein 9 (BRD9).

Pigment Cell Melanoma Res. 36, 19-32 (2023)
Verlagsversion Forschungsdaten DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Lineage-specific differentiation programs are activated by epigenetic changes in chromatin structure. Melanin-producing melanocytes maintain a gene expression program ensuring appropriate enzymatic conversion of metabolites into the pigment, melanin, and transfer to surrounding cells. During neuroectodermal development, SMARCA4 (BRG1), the catalytic subunit of SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes, is essential for lineage specification. SMARCA4 is also required for development of multipotent neural crest precursors into melanoblasts, which differentiate into pigment-producing melanocytes. In addition to the catalytic domain, SMARCA4 and several SWI/SNF subunits contain bromodomains which are amenable to pharmacological inhibition. We investigated the effects of pharmacological inhibitors of SWI/SNF bromodomains on melanocyte differentiation. Strikingly, treatment of murine melanoblasts and human neonatal epidermal melanocytes with selected bromodomain inhibitors abrogated melanin synthesis and visible pigmentation. Using functional genomics, iBRD9, a small molecule selective for the bromodomain of BRD9 was found to repress pigmentation-specific gene expression. Depletion of BRD9 confirmed a requirement for expression of pigmentation genes in the differentiation program from melanoblasts into pigmented melanocytes and in melanoma cells. Chromatin immunoprecipitation assays showed that iBRD9 disrupts the occupancy of BRD9 and the catalytic subunit SMARCA4 at melanocyte-specific loci. These data indicate that BRD9 promotes melanocyte pigmentation whereas pharmacological inhibition of BRD9 is repressive.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Brd9 ; Swi/snf ; Bromodomain ; Chromatin Remodeling ; Epigenetic ; Melanocyte Differentiation ; Melanoma ; Pigmentation
Sprache englisch
Veröffentlichungsjahr 2023
Prepublished im Jahr 2022
HGF-Berichtsjahr 2022
ISSN (print) / ISBN 1755-1471
e-ISSN 1755-148X
Zeitschrift Pigment Cell & Melanoma Research
Quellenangaben Band: 36, Heft: 1, Seiten: 19-32 Artikelnummer: , Supplement: ,
Verlag Wiley
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
POF Topic(s) 30205 - Bioengineering and Digital Health
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-503800-001
Förderungen Melanoma Research Foundation
DOI 10.1111/pcmr.13068
WOS ID WOS:000864144500001
Scopus ID 85139192033
PubMed ID 36112085
Erfassungsdatum 2022-11-24
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