Yeast Swd2 Is Essential Because of Antagonism between Set1 Histone Methyltransferase Complex and APT (Associated with Pta1) Termination Factor

The Set1 complex (also known as complex associated with Set1 or COMPASS) methylates histone H3 on lysine 4, with different levels of methylation affecting transcription by recruiting various factors to distinct regions of active genes. Neither Set1 nor its associated proteins are essential for viability with the notable exception of Swd2, a WD repeat protein that is also a subunit of the essential transcription termination factor APT (associated with Pta1). Cells lacking Set1 lose COMPASS recruitment but show increased promoter cross-linking of TFIIE large subunit and the serine 5 phosphorylated form of the Rpb1 C-terminal domain. Although Swd2 is normally required for bringing APT to genes, deletion of SET1 restores both viability and APT recruitment to a strain lacking Swd2. We propose a model in which Swd2 is required for APT to overcome antagonism by COMPASS. Background: The essential protein Swd2 is in both H3K4 methyltransferase complex Set1C/COMPASS and transcription termination factor APT. Results: Set1 deletion increases promoter cross-linking of the TFIIE large subunit and phosphorylated CTD, decreases COMPASS and Swd2, and suppresses lethality of Swd2 depletion. Conclusion: Set1-COMPASS affects early transcription and creates a requirement for Swd2 in APT recruitment. Significance: Swd2 may coordinate H3K4 methylation and early transcription termination.