Reference - PMID:41316862 - Deletion of Elongator Protein 1 (Elp1) relieves heterochromatin defects in a Pol II mutant of Schizosaccharomyces pombe.
Reference summary
- PubMed ID
- PMID:41316862
- Title
- Deletion of Elongator Protein 1 (Elp1) relieves heterochromatin defects in a Pol II mutant of Schizosaccharomyces pombe.
- Authors
- Nirmal MB, Pearce ME, Liu CT, Finkel JM, Darrow KS, Vo TV
- Citation
- Genetics 2025 Nov 29;
- Publication year
- 2025
- Abstract
- Heterochromatin is a repressive epigenetic state that suppresses transcription and safeguards genomic integrity. However, the full mechanism of its regulation remains elusive. Here, we focus on a previously described RNA polymerase II (Pol II) variant called m203 in Schizosaccharomyces pombe, which has a single substitution mutation within the Rpb2 subunit of Pol II (rpb2-N44Y) that reduces RNAi-dependent heterochromatin at a pericentromeric reporter locus. Through CRISPR-Cas9 site-directed mutagenesis, we find that rpb2-N44Y is a gain-of-function mutation. Furthermore, the heterochromatin defects of the m203 variant require a subunit of the Elongator complex called Elongator Protein 1 (Elp1), a protein that canonically promotes mcm5s2U34 tRNA modifications. While the single knockout of Elp1 in the m203 strain majorly restored heterochromatin formation, single knockouts of the Elp3 or the Elp5 subunits of Elongator showed only modest effects. Furthermore, mcm5s2 U34 tRNA modifications are dispensable for Elp1-dependent heterochromatin. In contrast, the heterochromatin required core factors that are critical for heterochromatin formation, including protein mediators of the RNA interference (RNAi) pathway and H3K9 methylation. Overall, our study reveals two distinct Rpb2-centric pathways, via RNAi or Elp1, that can positively or negatively regulate heterochromatin, respectively. Furthermore, our findings reveal a chromatin function for Elp1 that does not rely on Elongator-dependent mcm5s2U34 tRNA modifications. This work expands our understanding of how Elp1 can influence chromatin biology.
