| Swd2 (also known as Cps35 in budding yeast) is an essential WD‑repeat protein that serves as a shared component of the Set1/COMPASS histone H3K4 methyltransferase complex and the cleavage and polyadenylation factor (CPF), thereby linking transcription‑coupled chromatin modification to 3′‑end RNA processing in eukaryotes. The protein is built from multiple WD40 repeats that fold into a β‑propeller scaffold, and this structure provides a platform for simultaneous interaction with Set1 and other COMPASS subunits and with CPF components, positioning Swd2 as a structural and regulatory hub within both complexes. Swd2 is required for normal levels of H3K4 tri‑methylation at the 5′ regions of active genes and contributes to all H3K4 methylation states; loss or depletion of Swd2 destabilizes Set1, reduces COMPASS integrity, and markedly decreases H3K4me3, demonstrating that Swd2 is a positive determinant of Set1 catalytic activity and of proper distribution of H3K4 methyl marks along transcribed chromatin. Swd2 associates with elongating RNA polymerase II through CPF and the Paf1 complex and localizes to 3′ ends of genes, where CPF‑bound Swd2 participates in cleavage and polyadenylation of nascent pre‑mRNAs and contributes to proper termination of Pol II transcription, providing a mechanistic connection between elongation, co‑transcriptional mRNA 3′‑end formation, and downstream H3K4 methylation patterns across gene bodies. Dual membership of Swd2 in COMPASS and CPF allows the protein to coordinate 5′ H3K4 methylation status with 3′‑end processing efficiency, and Swd2 levels and complex occupancy show distinct requirements for viability and for full H3K4me3, indicating separable quantitative thresholds for its RNA‑processing and chromatin‑modifying functions. Swd2 also operates as a WD‑repeat β‑propeller adaptor that integrates the Rad6–H2Bub to H3K4me pathway with CPF‑dependent mRNA 3′‑end formation, enabling tight coupling of transcription, chromatin modification, and RNA maturation in yeast as a model for conserved eukaryotic gene‑expression control. |
