title: Arginine methylation of the histone H3 tail impedes effector binding.
abstract: Histone tail post-translational modification results in changes in cellular processes, either by generating or blocking docking sites for histone code readers or by altering the higher order chromatin structure. H3K4me3 is known to mark the promoter regions of active transcription. Proteins bind H3K4 in a methyl-dependent manner and aid in the recruitment of histone-remodeling enzymes and transcriptional cofactors. The H3K4me3 binders harbor methyl-specific chromatin binding domains, including plant homeodomain, Chromo, and tudor domains. Structural analysis of the plant homeodomains present in effector proteins, as well as the WD40 repeats of WDR5, reveals critical contacts between residues in these domains and H3R2. The intimate contact between H3R2 and these domain types leads to the hypothesis that methylation of this arginine residue antagonizes the binding of effector proteins to the N-terminal tail of H3. Here we show that H3 tail binding effector proteins are indeed sensitive to H3R2 methylation and that PRMT6, not CARM1/PRMT4, is the primary methyltransferase acting on this site. We have tested the expression of a select group of H3K4 effector-regulated genes in PRMT6 knockdown cells and found that their levels are altered. Thus, PRMT6 methylates H3R2 and is a negative regulator of N-terminal H3 tail binding.
authors: The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas 78957.
authors: Aimee N
authors: AN
authors: Iberg
authors: The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas 78957.
authors: Alexsandra
authors: A
authors: Espejo
authors: The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas 78957.
authors: Donghang
authors: D
authors: Cheng
authors: The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas 78957.
authors: Daehoon
authors: D
authors: Kim
authors: Terry Fox Molecular Oncology Group, McGill University, Montréal, Québec H3T 1E2, Canada.
authors: Jonathan
authors: J
authors: Michaud-Levesque
authors: Terry Fox Molecular Oncology Group, McGill University, Montréal, Québec H3T 1E2, Canada.
authors: Stephane
authors: S
authors: Richard
authors: The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas 78957. Electronic address: mtbedford@mdanderson.org.
authors: Mark T
authors: MT
authors: Bedford
mesh_terms: D000818:Animals; D001120:Arginine / Q000737:chemistry*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation; D006657:Histones / Q000737:chemistry*; D006801:Humans; D008745:Methylation; D009687:Nuclear Proteins / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011484:Protein-Arginine N-Methyltransferases / Q000737:chemistry; D012313:RNA / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D009687:Nuclear Proteins; D010455:Peptides; D012313:RNA; D001120:Arginine; C447833:PRMT6 protein, human; D011484:Protein-Arginine N-Methyltransferases