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
Telmo Henriques
Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Science, Durham, United States
Christopher A Lavender
Integrative Bioinformatics Support Group, National Institute of Environmental Health Science, Durham, United States
Daniel J McKay
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
Brian D Strahl
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
Robert J Duronio
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
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
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 in Drosophila to 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.
