We developed predictive models to explore the interaction between histone modifications and measures of transcription at promoters, distinguishing between modifications known to be added as a consequence of transcription (such as H3K36me3 and H3K79me2) and other categories of histone marks59. In our analyses, the best models had two components: an initial classification component (on/off) and a second quantitative model component. Our models showed activating acetylation marks (H3K27ac and H3K9ac) are roughly as informative as activating methylation marks (H3K4me3 and H3K4me2) (Figure 2A). Although repressive marks, such as H3K27me3 or H3K9me3, show negative correlation both individually and in the model, removing these marks produces only a small reduction in model performance. However, for a subset of promoters in each cell line repressive histone marks (H3K27me3 or H3K9me3) must be used to accurately predict their expression. We also examined the interplay between the H3K79me2 and H3K36me3 marks, both of which mark gene bodies, likely reflecting recruitment of modification enzymes by polymerase isoforms. As described previously, H3K79me2 occurs preferentially at the 5′ ends of gene bodies and H3K36me3 occurs more 3′, and our analyses support the previous model in which the H3K79me2 to H3K36me3 transition occurs at the first 3′ splice site60.
