SWI/SNF chromatin remodeling complex is critical for the expression of microphthalmia-associated transcription factor in melanoma cells
Abstract
The microphthalmia-associated transcription factor (MITF) is required for melanocyte development, maintenance of the melanocyte-specific transcription, and survival of melanoma cells. MITF positively regulates expression of more than 25 genes in pigment cells. Recently, it has been demonstrated that expression of several MITF downstream targets requires the SWI/SNF chromatin remodeling complex, which contains one of the two catalytic subunits, Brm or Brg1. Here we show that the expression of MITF itself critically requires active SWI/SNF. In several Brm/Brg1-expressing melanoma cell lines, knockdown of Brg1 severely compromised MITF expression with a concomitant downregulation of MITF targets and decreased cell proliferation. Although Brm was able to substitute for Brg1 in maintaining MITF expression and melanoma cell proliferation, sequential knockdown of both Brm and Brg1 in 501mel cells abolished proliferation. In Brg1-null SK-MEL-5 melanoma cells, depletion of Brm alone was sufficient to abrogate MITF expression and cell proliferation. Chromatin immunoprecipitation confirmed the binding of Brg1 or Brm to the promoter of MITF. Together these results demonstrate the essential role of SWI/SNF for expression of MITF and suggest that SWI/SNF may be a promissing target in melanoma therapy.
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MITF recruits critical components of the SWI/SNF chromatin remodeling complex (including SMARCA2) to the promoter region of its targets.
“MITF, the transcription factor known as the “master regulator of melanogenesis” due to its ability to activate many melanocyte-specific genes (Praetorius et al., 2013), recruits critical components of the SWI/SNF chromatin remodeling complex (including SMARCA2), to the promoter region of its targets (Vachtenheim et al., 2010).”
From An Unexpectedly Complex Architecture for Skin Pigmentation in Africans (2017) · cites this paper as Vachtenheim et al., 2010
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- Authors
- Vachtenheim, J., Ondrušová, L., & Borovanský, J.
- Affiliations
- Charles University (CZ)
- Corresponding author
- Vachtenheim, Jiri
- ORCID
- Vachtenheim, Jiri
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 392
- Issue
- 3
- Pages
- 454-459
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W1983179216
- Cited by
- 48
- References
- 37
- Citations by year
- 2026: 1 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 5 · 2018: 3 · 2017: 5 · 2016: 2 · 2015: 6 · 2014: 5 · 2013: 7 · 2012: 1
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Update notices
- erratum (2010-05-14)
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- IGA MZ (NR/9319-3)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- SWI/SNF complex, microphthalmia-associated transcription factor, MITF, melanoma, SMARCA4, BRM, transcriptional regulation, melanoma cell proliferation, promoter binding, melanocyte development, therapeutic target
- MeSH terms
- Chromosomal Proteins, Non-Histone, DNA Helicases, Humans, Melanoma, Nuclear Proteins, Promoter Regions, Genetic, Transcription Factors, Transcriptional Activation, Gene Expression Regulation, Neoplastic, Chromatin Assembly and Disassembly, Cell Line, Tumor, Immunoprecipitation, Microphthalmia-Associated Transcription Factor
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