ArticlePloS one2017
Sequence-specific DNA binding by MYC/MAX to low-affinity non-E-box motifs.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 61 citations in OpenAlex.
- RegRegSEA: a web server for regulatory region set enrichment analysis of epigenomic data.Nucleic acids research · 2026Article
- Probing the Structural Dynamics of the Unbound MAX Protein: Insights from Well-Tempered Metadynamics.Journal of chemical information and modeling · 2026Article
- MYC as a key target for melanoma therapy.Frontiers in cell and developmental biology · 2026Review
- Role of circadian CLOCK signaling in cellular senescence.Biogerontology · 2025Review
- MYC Binding Near Transcriptional End Sites Regulates Basal Gene Expression, Read-Through Transcription, and Intragenic Contacts.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The relationship between acid-sensing ion channel, ASIC2, and oncogenic β-catenin signaling in ovarian cancer.Scientific reports · 2025Article
- Mutations to transcription factor MAX allosterically increase DNA selectivity by altering folding and binding pathways.Nature communications · 2025Article
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- Article
- Transcriptional Targets of TWIST1 in Human Mesenchymal Stem/Stromal Cells Mechanistically Link Stem/Progenitor and Paracrine Functions.Stem cells (Dayton, Ohio) · 2023Article
- CRISPR/Cas9 screen for genome-wide interrogation of essential MYC-bound E-boxes in cancer cells.Molecular oncology · 2023Article
- Design and Characterization of pMyc/pMax Peptide-Coupled Gold Nanosystems for Targeting Myc in Prostate Cancer Cell Lines.Nanomaterials (Basel, Switzerland) · 2023Article
- MYC acetylated lysine residues drive oncogenic cell transformation and regulate select genetic programs for cell adhesion-independent growth and survival.Genes & development · 2023Article
- Review
- Investigating In Situ Expression of c-MYC and Candidate Ubiquitin-Specific Proteases in DLBCL and Assessment for Peptidyl Disruptor Molecule against c-MYC-USP37 Complex.Molecules (Basel, Switzerland) · 2023Article
- Article
- Lysosomes: multifunctional compartments ruled by a complex regulatory network.FEBS open bio · 2022Review
- EZH2 noncanonically binds cMyc and p300 through a cryptic transactivation domain to mediate gene activation and promote oncogenesis.Nature cell biology · 2022Article
- Epigenetic Silencing of 15-Hydroxyprostaglandin Dehydrogenase by Histone Methyltransferase EHMT2/G9a in Cholangiocarcinoma.Molecular cancer research : MCR · 2022Article
- Regulation of Human Papillomavirus 18 Genome Replication, Establishment, and Persistence by Sequences in the Viral Upstream Regulatory Region.Journal of virology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The MYC oncoprotein regulates transcription of a large fraction of the genome as an obligatory heterodimer with the transcription factor MAX. The MYC:MAX heterodimer and MAX:MAX homodimer (hereafter MYC/MAX) bind Enhancer box (E-box) DNA elements (CANNTG) and have the greatest affinity for the canonical MYC E-box (CME) CACGTG. However, MYC:MAX also recognizes E-box variants and was reported to bind DNA in a "non-specific" fashion in vitro and in vivo. Here, in order to identify potential additional non-canonical binding sites for MYC/MAX, we employed high throughput in vitro protein-binding microarrays, along with electrophoretic mobility-shift assays and bioinformatic analyses of MYC-bound genomic loci in vivo. We identified all hexameric motifs preferentially bound by MYC/MAX in vitro, which include the low-affinity non-E-box sequence AACGTT, and found that the vast majority (87%) of MYC-bound genomic sites in a human B cell line contain at least one of the top 21 motifs bound by MYC:MAX in vitro. We further show that high MYC/MAX concentrations are needed for specific binding to the low-affinity sequence AACGTT in vitro and that elevated MYC levels in vivo more markedly increase the occupancy of AACGTT sites relative to CME sites, especially at distal intergenic and intragenic loci. Hence, MYC binds diverse DNA motifs with a broad range of affinities in a sequence-specific and dose-dependent manner, suggesting that MYC overexpression has more selective effects on the tumor transcriptome than previously thought.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.