2PNX

The PHD finger of ING4 in complex with an H3K4Me3 histone peptide

Summary for 2PNX

• Entry DOI: 10.2210/pdb2pnx/pdb
• Descriptor: Inhibitor of growth protein 4, H3K4Me3 peptide, ZINC ION, ... (4 entities in total)
• Functional Keywords: protein-peptide complex, chromatin, zinc finger, histone, gene regulation
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q9UNL4
• Total number of polymer chains: 4
• Total formula weight: 15555.05

Authors

Champagne, K.S.,Johnson, K.,Kutateladze, T.G. (deposition date: 2007-04-25, release date: 2008-04-15, Last modification date: 2025-03-26)

Primary citation

Hung, T.,Binda, O.,Champagne, K.S.,Kuo, A.J.,Johnson, K.,Chang, H.Y.,Simon, M.D.,Kutateladze, T.G.,Gozani, O.
ING4 mediates crosstalk between histone H3 K4 trimethylation and H3 acetylation to attenuate cellular transformation
Mol.Cell, 33:248-256, 2009

PubMed Abstract: Aberrations in chromatin dynamics play a fundamental role in tumorigenesis, yet relatively little is known of the molecular mechanisms linking histone lysine methylation to neoplastic disease. ING4 (Inhibitor of Growth 4) is a native subunit of an HBO1 histone acetyltransferase (HAT) complex and a tumor suppressor protein. Here we show a critical role for specific recognition of histone H3 trimethylated at lysine 4 (H3K4me3) by the ING4 PHD finger in mediating ING4 gene expression and tumor suppressor functions. The interaction between ING4 and H3K4me3 augments HBO1 acetylation activity on H3 tails and drives H3 acetylation at ING4 target promoters. Further, ING4 facilitates apoptosis in response to genotoxic stress and inhibits anchorage-independent cell growth, and these functions depend on ING4 interactions with H3K4me3. Together, our results demonstrate a mechanism for brokering crosstalk between H3K4 methylation and H3 acetylation and reveal a molecular link between chromatin modulation and tumor suppressor mechanisms.

PubMed: 19187765
DOI: 10.1016/j.molcel.2008.12.016

Experimental method

X-RAY DIFFRACTION (1.8 Å)