Recent transcription-induced histone H3 lysine 4 (H3K4) methylation inhibits gene reactivation.

Recent transcription of GAL genes transiently leaves an H3K4 methylation mark at their promoters, providing an epigenetic memory for the recent transcriptional activity. However, the physiological significance of this mark is enigmatic. In our study, we show that the transient H3K4 di- and trimethylation at recently transcribed GAL1 inhibited the reinduction of GAL1. The H3K4 methylation functioned by recruiting the Isw1 ATPase onto GAL1 and thereby limiting the action of RNA polymerase II during GAL1 reactivation. Strikingly, the H3K4 methylation was also observed at the promoters of inositol- and fatty acid-responsive genes after recent transcription and played a negative role in their reinduction. Taken together, our data present a new mechanism by which H3K4 methylation regulates gene transcription.