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. Author manuscript; available in PMC: 2014 Mar 7.
Published in final edited form as: Mol Cell. 2013 Mar 7;49(5):10.1016/j.molcel.2013.01.038. doi: 10.1016/j.molcel.2013.01.038

Figure 3.

Figure 3

Methylation of H3K4 at enhancers and promoters (A) Enhancers and promoters can be distinguished by the methylation status at the histone H3 lysine 4 (H3K4). Enhancers are enriched for H3K4me1, whereas high levels of H3K4me3 predominantly mark promoters. These differences can be largely explained by the underlying differences in DNA sequence, with high CpG island density observed at most promoters, but not at enhancers. CpG-rich regions are recognized by the CxxC domain of Cfp1, a specific subunit of Set1a/b complex, allowing for its preferential binding and H3K4me3 at promoters. In contrast, other methyltransferases, such as Trr/MLL3/MLL4 complex are likely responsible for H3K4me1 at enhancers. (B) Point mutation in the CxxC motif of Cpf1, which disrupts CpG island recognition, but not the complex assembly, alters binding specificity of the Set1a/b complex, resulting in the ectopic deposition of H3K4me3 at enhancers, leading in turn to aberrantly increased transcriptional activity at the enhancer and, commonly, also at the nearby promoter. See text for details.