ArticleNucleic acids research2017
MAX is an epigenetic sensor of 5-carboxylcytosine and is altered in multiple myeloma.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group.Molecular psychiatry · 2021Pooled it
- Relationship between Prostate Cancer and Benign Hyperplasia: Role of Inflammation-Induced Oxidative Stress, Vitamin C, and Epigenetics.The world journal of men's health · 2026Review
- Changes in active DNA demethylation pathway components during neoadjuvant chemotherapy and their prognostic significance in breast cancer.Breast cancer research : BCR · 2026Article
- Detection of the Heterozygous Recurrent MAX p.(Arg60Gln) Variant in Two Females Confirms and Expands the Phenotypic Spectrum of Polydactyly-Macrocephaly Syndrome.Clinical genetics · 2026Article
- Mammalian Proteome Profiling Reveals Readers and Antireaders of Strand-Symmetric and -Asymmetric 5-Hydroxymethylcytosine-Modifications in DNA.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The role of cytosine modification symmetry in mammalian epigenome regulation.Chemical science · 2026Review
- DBP-CanPred: a machine learning model for predicting cancer-causing mutations in DNA-binding proteins.Frontiers in bioinformatics · 2026Article
- Extramedullary myeloma is genomically complex and characterized by near-universal MAPK pathway alterations.Blood advances · 2025Article
- Mutations to transcription factor MAX allosterically increase DNA selectivity by altering folding and binding pathways.Nature communications · 2025Article
- Selective Enhancer Gain-of-Function Deregulates MYC Expression in Multiple Myeloma.Cancer research · 2024Article
- Epigenetic DNA modifications and vitamin C in prostate cancer and benign prostatic hyperplasia: Exploring similarities, disparities, and pathogenic implications.Neoplasia (New York, N.Y.) · 2024Article
- DNA-binding proteins from MBD through ZF to BEN: recognition of cytosine methylation status by one arginine with two conformations.Nucleic acids research · 2024Article
- Epigenetic regulation of innate immune dynamics during inflammation.Journal of leukocyte biology · 2024Review
- The Genetic and Molecular Drivers of Multiple Myeloma: Current Insights, Clinical Implications, and the Path Forward.Pharmacogenomics and personalized medicine · 2024Review
- Structural basis for specific DNA sequence motif recognition by the TFAP2 transcription factors.Nucleic acids research · 2023Article
- Biochemical and structural characterization of the first-discovered metazoan DNA cytosine-N4 methyltransferase from the bdelloid rotifer Adineta vaga.The Journal of biological chemistry · 2023Article
- Article
- Physicochemical models of protein-DNA binding with standard and modified base pairs.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Aberrant DNA hydroxymethylation reshapes transcription factor binding in myeloid neoplasms.Clinical epigenetics · 2022Article
- Mechanisms that regulate the activities of TET proteins.Cellular and molecular life sciences : CMLS · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The oncogenic transcription factor MYC and its binding partner MAX regulate gene expression by binding to DNA at enhancer-box (E-box) elements 5΄-CACGTG-3΄. In mammalian genomes, the central E-box CpG has the potential to be methylated at the 5-position of cytosine (5mC), or to undergo further oxidation to the 5-hydroxymethyl (5hmC), 5-formyl (5fC), or 5-carboxyl (5caC) forms. We find that MAX exhibits the greatest affinity for a 5caC or unmodified C-containing E-box, and much reduced affinities for the corresponding 5mC, 5hmC or 5fC forms. Crystallization of MAX with a 5caC modified E-box oligonucleotide revealed that MAX Arg36 recognizes 5caC using a 5caC-Arg-Guanine triad, with the next nearest residue to the carboxylate group being Arg60. In an analysis of >800 primary multiple myelomas, MAX alterations occurred at a frequency of ∼3%, more than half of which were single nucleotide substitutions affecting a basic clamp-like interface important for DNA interaction. Among these, arginines 35, 36 and 60 were the most frequently altered. In vitro binding studies showed that whereas mutation of Arg36 (R36W) or Arg35 (R35H/L) completely abolished DNA binding, mutation of Arg60 (R60Q) significantly reduced DNA binding, but retained a preference for the 5caC modified E-box. Interestingly, MAX alterations define a subset of myeloma patients with lower MYC expression and a better overall prognosis. Together these data indicate that MAX can act as a direct epigenetic sensor of E-box cytosine modification states and that local CpG modification and MAX variants converge to modulate the MAX-MYC transcriptional network.
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Registered trials
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.