Journal article
PAX3 Regulatory Signatures and Gene Targets in Melanoma Cells
Genes, Vol.16(5), 577
05/14/2025
DOI: 10.3390/genes16050577
PMCID: PMC12111051
PMID: 40428399
Abstract
Background/Objectives: PAX3 is a transcription factor that drives melanoma progression by promoting cell growth, migration, and survival, while inhibiting cellular terminal differentiation. However, known PAX3 target genes are limited and cannot fully explain the wide impact of PAX3 function. The PAX3 protein can regulate DNA through two separate binding domains, the Paired Domain (PD) and Homeodomain (HD), which bind different DNA motifs. It is not clear if these two domains bind and work together to regulate genes and if they promote all or only a subset of downstream cellular events. Methods: PAX3 direct downstream targets were identified using Cleavage Under Targets & Release Using Nuclease (CUT&RUN) assays in SK-MEL-5 melanoma cells. PAX3-binding genomic regions were identified through MACS2 peak calling, and peaks were categorized based on the presence of PD and/or HD binding sites (or neither) through HOMER motif analysis. The peaks were further characterized as Active, Primed, Poised, Repressed, or Closed based on ATAC-seq data and CUT&RUN for histone Post-Translational Modifications H3K4me1, H3K4me3, H3K27me3, and H3K27Ac. Results: This analysis revealed that most of the PAX3 binding sites in the SK-MEL-5 cell line were primarily through the PD and connected to Active genes. Surprisingly, PAX3 does not commonly act as a repressor in SK-MEL-5 cells. Pathway analysis identified genes involved with transcription, RNA modification, and cell growth. Peaks located in distal enhancer elements were connected to genes involved in neuronal growth, function, and signaling. Conclusions: Our results reveal novel PAX3 regulatory regions and putative genes in a melanoma cell line, with a predominance of PAX3 PD binding on active sites.
Details
- Title: Subtitle
- PAX3 Regulatory Signatures and Gene Targets in Melanoma Cells
- Creators
- Stephen P. G. Moore - Boston UniversityShripushkar Ganesh Krishnan - Boston UniversityRutu Jaswanth Kothari - Boston UniversityNoah B. Prince - Boston UniversityColin Kenny - University of IowaChao Zhang - Boston UniversityDeborah Lang - Boston University
- Resource Type
- Journal article
- Publication Details
- Genes, Vol.16(5), 577
- DOI
- 10.3390/genes16050577
- PMID
- 40428399
- PMCID
- PMC12111051
- NLM abbreviation
- Genes (Basel)
- ISSN
- 2073-4425
- eISSN
- 2073-4425
- Publisher
- MDPI
- Grant note
- Leo FoundationAmerican Cancer Society: DBG-23-1152683-01-RMC, TLC-24-1345883-01-TLC, IRG-22-153-42-IRG-07 National Institutes of Health/National Cancer Institute: 1R03CA288281-01A1 National Institutes of Health/National Center for Advancing Translational Sciences: 1TL1TR001410, 1UL1TR001430 Boston University Genome Science Institute (GSI) pilot project program
This research was funded by the Leo Foundation, LF-OC-21-00088; The American Cancer Society, DBG-23-1152683-01-RMC, TLC-24-1345883-01-TLC, and IRG-22-153-42-IRG-07; The National Institutes of Health/National Cancer Institute, 1R03CA288281-01A1, The National Institutes of Health/National Center for Advancing Translational Sciences and the Boston University Clinical and Translational Science Institute 1TL1TR001410 and 1UL1TR001430, and the Boston University Genome Science Institute (GSI) pilot project program.
- Language
- English
- Date published
- 05/14/2025
- Academic Unit
- Anatomy and Cell Biology; Surgery
- Record Identifier
- 9984824291402771
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