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MYC in Epigenetics and Disease

The MYC protein family consists of transcription factors that bind DNA at E-box motifs. These proteins promote cell growth and proliferation, can contribute to cancer when dysregulated, and require the partner protein MAX (MYC-associated factor X) to function. The MYC gene family includes three main members: c-Myc, N-Myc, and L-Myc.

c-Myc (cellular myelocytomatosis) is a master regulator of cell growth, proliferation, and metabolism. It is the most widely studied member of the family and the one most commonly altered in cancer. N-Myc regulates neural development and is highly expressed in early embryonic and neuronal tissues. L-Myc plays important roles in lung tissue and certain immune cells, with functional overlap but generally weaker activity compared to c-Myc.

All MYC family members form dimers with MAX to bind DNA. MAX itself is a transcription factor that partners with different proteins to regulate whether genes are turned on or off. When MYC dimerizes with MAX, the MYC–MAX complex binds DNA and activates genes related to cell growth, metabolism, and cell cycle progression. MAX is broadly expressed across many tissues because MYC-family regulation is essential in most cell types.

 
Protein / Family Epigenetic Function Disease Association Key Publications Key Products
BRD4 BET protein that binds acetylated chromatin, stabilizes MYC transcription. MYC-driven cancers (NUT carcinoma, AML). Chen et al., World J Gastroenterol. 2025
c-Myc (MYC) Transcription factor. Regulates genes controlling cell growth, metabolism, and ribosome biogenesis. Many cancers (lymphoma, breast, colon, lung), metabolic disorders. Thumpati et al., Sci Pharm. 2025
CDK9 (P-TEFb complex) Supports MYC-driven transcriptional elongation. Leukemias, lymphomas. Wu et al., Mol. Oncol. 2025
EZH2 (PRC2 complex) Represses differentiation genes while MYC activates growth genes. Lymphomas, prostate cancer. Huang et al., Acta Pharmacol. Sin. 2025
GCN5 / KAT2A Histone acetyltransferase recruited by c-Myc–TRRAP. Leukemias, lymphomas, and solid tumors. Cirigliano et al., Int. J. Mol. Sci. 2025
GSK3β Kinase that phosphorylates MYC, marking it for degradation. Colorectal cancer, neurodegeneration. Liu et al., Commun. Biol. 2025
HDAC1/2 Histone deacetylases recruited by MAD/MXD proteins; oppose MYC activity. Cancers with transcriptional repression defects. MYC-driven tumors. Chen et al., Mol. Pharmacol. Drug Resist.: Lymphoid Neoplasms. 2025
MAD/MXD family (MXD1, MXI1, MNT) Antagonists of c-Myc. Compete for MAX binding. Repress target genes. Recruit histone deacetylases (HDACs) to promote transcriptional repression. MYC-amplified cancers. MXI1 deletions linked to prostate cancer. Qu et al., Nat. Commun. 2025
MAX Heterodimer partner for c-Myc. Required for DNA binding. Recruits histone acetyltransferases (HATs). MYC-driven cancers, MAX-driven tumors (pheochromocytoma). Obisesan et al., J. Med. Chem. 2025
p300 / CBP Transcriptional co-activators. Interact with MYC and add acetyl groups to histones and MYC itself. Various solid tumors and hematologic cancers. Chen et al., Neoplasia. 2025
PCAF / KAT2B HAT that can act redundantly with GCN5; MYC co-activator. Cancers with epigenetic dysregulation. Lin et al., Cell Death Dis. 2025
SIN3A Corepressor that partners with MAD/MXD and HDACs to repress MYC target genes. Breast cancer, leukemias. Dong et al., Transl Cancer Res. 2025
TIP60 (KAT5) HAT involved in DNA damage response; interacts with MYC complexes. Breast cancer, prostate cancer, lymphomas. Sheng et al., Bull. Cancer. 2025

 

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