3U5O

Crystal structure of the complex of TRIM33 PHD-Bromo and H3(1-22)K9me3K14acK18ac histone peptide

Summary for 3U5O

• Entry DOI: 10.2210/pdb3u5o/pdb
• Related: 3U5M 3U5N 3U5P
• Descriptor: E3 ubiquitin-protein ligase TRIM33, Histone H3.1, ZINC ION (3 entities in total)
• Functional Keywords: trim33, phd, bromodomain, tgf-beta, epigenetics, histone, methylation, k9me3, k14ac, k18ac, transcription
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q9UPN9 P68431
• Total number of polymer chains: 16
• Total formula weight: 211583.78

Authors

Wang, Z.,Patel, D.J. (deposition date: 2011-10-11, release date: 2012-01-18, Last modification date: 2023-12-06)

Primary citation

Xi, Q.,Wang, Z.,Zaromytidou, A.I.,Zhang, X.H.,Chow-Tsang, L.F.,Liu, J.X.,Kim, H.,Barlas, A.,Manova-Todorova, K.,Kaartinen, V.,Studer, L.,Mark, W.,Patel, D.J.,Massague, J.
A poised chromatin platform for TGF-beta access to master regulators
Cell(Cambridge,Mass.), 147:1511-1524, 2011

PubMed Abstract: Specific chromatin marks keep master regulators of differentiation silent yet poised for activation by extracellular signals. We report that nodal TGF-β signals use the poised histone mark H3K9me3 to trigger differentiation of mammalian embryonic stem cells. Nodal receptors induce the formation of companion Smad4-Smad2/3 and TRIM33-Smad2/3 complexes. The PHD-Bromo cassette of TRIM33 facilitates binding of TRIM33-Smad2/3 to H3K9me3 and H3K18ac on the promoters of mesendoderm regulators Gsc and Mixl1. The crystal structure of this cassette, bound to histone H3 peptides, illustrates that PHD recognizes K9me3, and Bromo binds an adjacent K18ac. The interaction between TRIM33-Smad2/3 and H3K9me3 displaces the chromatin-compacting factor HP1γ, making nodal response elements accessible to Smad4-Smad2/3 for Pol II recruitment. In turn, Smad4 increases K18 acetylation to augment TRIM33-Smad2/3 binding. Thus, nodal effectors use the H3K9me3 mark as a platform to switch master regulators of stem cell differentiation from the poised to the active state.

PubMed: 22196728
DOI: 10.1016/j.cell.2011.11.032

Experimental method

X-RAY DIFFRACTION (2.7 Å)