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

Epigenetics & Chromatin
Archit TrivediIvana L de la Serna

Abstract

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. 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...Continue Reading

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Citations

Aug 14, 2021·Beilstein Journal of Organic Chemistry·Renato L CarvalhoEufrânio N da Silva Júnior

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Datasets Mentioned

BETA
GSM2527370
GSM2700494

Methods Mentioned

BETA
Flow Cytometry
Flow
PCR
RNA-seq
ChIP-seq
immunoprecipitation
ChIPs
ChIP
co-immunoprecipitation
acetylation

Software Mentioned

ChIPpeakAnno
Ensembl homog
RStudio
Tophat2
GeneCards
Bioconductor
Ensembl
Graphpad Prism
Scepter
SDS

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