title: Histone gene replacement reveals a post-transcriptional role for H3K36 in maintaining metazoan transcriptome fidelity.
abstract: Histone H3 lysine 36 methylation (H3K36me) is thought to participate in a host of co-transcriptional regulatory events. To study the function of this residue independent from the enzymes that modify it, we used a 'histone replacement' system inDrosophilato generate a non-modifiable H3K36 lysine-to-arginine (H3K36R) mutant. We observed global dysregulation of mRNA levels in H3K36R animals that correlates with the incidence of H3K36me3. Similar to previous studies, we found that mutation of H3K36 also resulted in H4 hyperacetylation. However, neither cryptic transcription initiation, nor alternative pre-mRNA splicing, contributed to the observed changes in expression, in contrast with previously reported roles for H3K36me. Interestingly, knockdown of the RNA surveillance nuclease, Xrn1, and members of the CCR4-Not deadenylase complex, restored mRNA levels for a class of downregulated, H3K36me3-rich genes. We propose a post-transcriptional role for modification of replication-dependent H3K36 in the control of metazoan gene expression.
authors.affiliation: Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, United States.|Integrative Program for Biological and Genome Sciences, The University of North Carolina at Chapel Hill, Chapel Hill, United States.
authors.forename: Michael P
authors.identifier: 0000-0003-3438-3938
authors.initials: MP
authors.lastname: Meers
authors.affiliation: Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Science, Durham, United States.
authors.forename: Telmo
authors.initials: T
authors.lastname: Henriques
authors.affiliation: Integrative Bioinformatics Support Group, National Institute of Environmental Health Science, Durham, United States.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lavender
authors.affiliation: Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, United States.|Integrative Program for Biological and Genome Sciences, The University of North Carolina at Chapel Hill, Chapel Hill, United States.|Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, United States.|Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, United States.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: McKay
authors.affiliation: Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, United States.|Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Strahl
authors.affiliation: Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, United States.|Integrative Program for Biological and Genome Sciences, The University of North Carolina at Chapel Hill, Chapel Hill, United States.|Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, United States.|Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, United States.|Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Duronio
authors.affiliation: Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Science, Durham, United States.
authors.forename: Karen
authors.identifier: 0000-0001-5364-334X
authors.initials: K
authors.lastname: Adelman
authors.affiliation: Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, United States.|Integrative Program for Biological and Genome Sciences, The University of North Carolina at Chapel Hill, Chapel Hill, United States.|Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, United States.|Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, United States.|Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States.
authors.forename: A Gregory
authors.identifier: 0000-0002-6406-0630
authors.initials: AG
authors.lastname: Matera
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D004330:Drosophila; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D020125:Mutation, Missense; D011499:Protein Processing, Post-Translational; D014158:Transcription, Genetic
chemical_list: D006657:Histones
keywords: D. melanogaster; RNA; chromosomes; epigenetics; evolutionary biology; genes; genomics; splicing