RT Journal Article
SR Electronic
T1 Histone gene replacement reveals a post-transcriptional role for H3K36 in maintaining metazoan transcriptome fidelity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 114926
DO 10.1101/114926
A1 Michael P. Meers
A1 Telmo Henriques
A1 Christopher A. Lavender
A1 Daniel J. McKay
A1 Brian D. Strahl
A1 Robert J. Duronio
A1 Karen Adelman
A1 A. Gregory Matera
YR 2017
UL http://biorxiv.org/content/early/2017/03/08/114926.abstract
AB 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 posttranscriptional role for modification of replication-dependent H3K36 in the control of metazoan gene expression.Impact Statement Post-translational modification of histone H3K36 is neither required to suppress cryptic transcription initiation nor to include alternative exons in Drosophila; instead it promotes expression of active genes by stimulating polyadenylation.