Biomaterial Database

Enzymatic nucleosome acetylation selectively affects activity of histone methyltransferases in vitro. 2022

Viacheslav V Trush, and Christian Feller, and Alice Shi Ming Li, and Abdellah Allali-Hassani, and Magdalena M Szewczyk, and Irene Chau, and Mohammad S Eram, and Boya Jiang, and Raymond Luu, and Fangfei Zhang, and Dalia Barsyte-Lovejoy, and Ruedi Aebersold, and Cheryl H Arrowsmith, and Masoud Vedadi

Structural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.

Posttranslational modification of histones plays a critical role in regulation of gene expression. These modifications include methylation and acetylation that work in combination to establish transcriptionally active or repressive chromatin states. Histone methyltransferases (HMTs) often have variable levels of activity in vitro depending on the form of substrate used. For example, certain HMTs prefer nucleosomes extracted from human or chicken cells as substrate compared to recombinant nucleosomes reconstituted from bacterially produced histones. We considered that pre-existing histone modifications in the extracted nucleosomes can affect the efficiency of catalysis by HMTs, suggesting functional cross-talk between histone-modifying enzymes within a complex network of interdependent activities. Here we systematically investigated the effect of nucleosome acetylation by EP300, GCN5L2 (KAT2A) and MYST1 (MOF) on histone 3 lysine 4 (H3K4), H3K9 and H4K20 methylation of nucleosomes by nine HMTs (MLL1, MLL3, SET1B, G9a, SETDB1, SUV39H1, SUV39H2, SUV420H1 and SUV420H2) in vitro. Our full kinetic characterization data indicate that site-specific acetylation of nucleosomal histones by specific acetyltransferases can create nucleosomes that are better substrates for specific HMTs. This includes significant increases in catalytic efficiencies of SETDB1, G9a and SUV420H2 after nucleosome acetylation in vitro.

UI	MeSH Term	Description	Entries
D009707	Nucleosomes	The repeating structural units of chromatin, each consisting of approximately 200 base pairs of DNA wound around a protein core. This core is composed of the histones H2A, H2B, H3, and H4.	Dinucleosomes,Polynucleosomes,Dinucleosome,Nucleosome,Polynucleosome
D011499	Protein Processing, Post-Translational	Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.	Amino Acid Modification, Post-Translational,Post-Translational Modification,Post-Translational Protein Modification,Posttranslational Modification,Protein Modification, Post-Translational,Amino Acid Modification, Posttranslational,Post-Translational Amino Acid Modification,Post-Translational Modifications,Post-Translational Protein Processing,Posttranslational Amino Acid Modification,Posttranslational Modifications,Posttranslational Protein Processing,Protein Processing, Post Translational,Protein Processing, Posttranslational,Amino Acid Modification, Post Translational,Modification, Post-Translational,Modification, Post-Translational Protein,Modification, Posttranslational,Modifications, Post-Translational,Modifications, Post-Translational Protein,Modifications, Posttranslational,Post Translational Amino Acid Modification,Post Translational Modification,Post Translational Modifications,Post Translational Protein Modification,Post Translational Protein Processing,Post-Translational Protein Modifications,Processing, Post-Translational Protein,Processing, Posttranslational Protein,Protein Modification, Post Translational,Protein Modifications, Post-Translational
D006657	Histones	Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.	Histone,Histone H1,Histone H1(s),Histone H2a,Histone H2b,Histone H3,Histone H3.3,Histone H4,Histone H5,Histone H7
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000076983	Histone Methyltransferases	Enzymes that catalyze the transfer of methyl groups to LYSINE or ARGININE residues of HISTONES, especially histone H3 and histone H4 proteins. They play a critical role in EPIGENETIC PROCESSES.	Histone H3 Methyltransferase,Histone Methylase,Histone Methyltransferase,Histone-Arginine N-Methyltransferase,H3 Methyltransferase, Histone,Histone Arginine N Methyltransferase,Methylase, Histone,Methyltransferase, Histone,Methyltransferase, Histone H3,Methyltransferases, Histone,N-Methyltransferase, Histone-Arginine
D000107	Acetylation	Formation of an acetyl derivative. (Stedman, 25th ed)	Acetylations