Determinants of Histone H3K4 Methylation Patterns

다국어 초록 (Multilingual Abstract)

<P><B>Summary</B></P> <P>Various factors differentially recognize trimethylated histone H3 lysine 4 (H3K4me3) near promoters, H3K4me2 just downstream, and promoter-distal H3K4me1 to modulate gene expression. This methylation “gradient” is thought to result from preferential binding of the H3K4 methyltransferase Set1/complex associated with Set1 (COMPASS) to promoter-proximal RNA polymerase II. However, other studies have suggested that location-specific cues allosterically activate Set1. Chromatin immunoprecipitation sequencing (ChIP-seq) experiments show that H3K4 methylation patterns on active genes are not universal or fixed and change in response to both transcription elongation rate and frequency as well as reduced COMPASS activity. Fusing Set1 to RNA polymerase II results in H3K4me2 throughout transcribed regions and similarly extended H3K4me3 on highly transcribed genes. Tethered Set1 still requires histone H2B ubiquitylation for activity. These results show that higher-level methylations reflect not only Set1/COMPASS recruitment but also multiple rounds of transcription. This model provides a simple explanation for non-canonical methylation patterns at some loci or in certain COMPASS mutants.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Many genes do not show the canonical H3K4 methylation gradient pattern </LI> <LI> H3K4 methylation levels are determined by the time Set1 spends near the nucleosome </LI> <LI> Multiple rounds of transcription contribute to H3K4 trimethylation levels </LI> <LI> Set1 fused to RNA pol II places H3K4me2 and H3K4me3 throughout transcribed regions </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>