HDAC2 Is Involved in the Regulation of BRN3A in Melanocytes and Melanoma

Heppt M, Wessely A, Hornig E, Kammerbauer C, Graf SA, Besch R, French LE, Matthies AO, Kuphal S, Kappelmann-Fenzl M, Boßerhoff AK, Berking C (2022)

Publication Type: Journal article

Publication year: 2022

Journal

International Journal of Molecular Sciences MDPI

Book Volume: 23

Article Number: 849

Journal Issue: 2

DOI: 10.3390/ijms23020849

Abstract

The neural crest transcription factor BRN3A is essential for the proliferation and survival of melanoma cells. It is frequently expressed in melanoma but not in normal melanocytes or benign nevi. The mechanisms underlying the aberrant expression of BRN3A are unknown. Here, we investigated the epigenetic regulation of BRN3A in melanocytes and melanoma cell lines treated with DNA methyltransferase (DNMT), histone acetyltransferase (HAT), and histone deacetylase (HDAC) inhibitors. DNMT and HAT inhibition did not significantly alter BRN3A expression levels, whereas panHDAC inhibition by trichostatin A led to increased expression. Treatment with the isoform-specific HDAC inhibitor mocetinostat, but not with PCI-34051, also increased BRN3A expression levels, suggesting that class I HDACs HDAC1, HDAC2, and HDAC3, and class IV HDAC11, were involved in the regulation of BRN3A expression. Transient silencing of HDACs 1, 2, 3, and 11 by siRNAs revealed that, specifically, HDAC2 inhibition was able to increase BRN3A expression. ChIP-Seq analysis uncovered that HDAC2 inhibition specifically increased H3K27ac levels at a distal enhancer region of the BRN3A gene. Altogether, our data suggest that HDAC2 is a key epigenetic regulator of BRN3A in melanocytes and melanoma cells. These results highlight the importance of epigenetic mechanisms in regulating melanoma oncogenes.

Authors with CRIS profile

Markus Heppt Department of Dermatology Alexander Oliver Matthies Lehrstuhl für Biochemie und Molekulare Medizin Silke Kuphal Medizinische Fakultät Anja Katrin Boßerhoff Lehrstuhl für Biochemie und Molekulare Medizin Carola Berking Lehrstuhl für Haut- und Geschlechtskrankheiten

Involved external institutions

Klinikum der Universität München DE Germany (DE) Technische Hochschule Deggendorf DE Germany (DE)

How to cite

APA:

Heppt, M., Wessely, A., Hornig, E., Kammerbauer, C., Graf, S.A., Besch, R.,... Berking, C. (2022). HDAC2 Is Involved in the Regulation of BRN3A in Melanocytes and Melanoma. International Journal of Molecular Sciences, 23(2). https://dx.doi.org/10.3390/ijms23020849

MLA:

Heppt, Markus, et al. "HDAC2 Is Involved in the Regulation of BRN3A in Melanocytes and Melanoma." International Journal of Molecular Sciences 23.2 (2022).

BibTeX: Download