AI Article Synopsis
- - Complex associating with SET1 (COMPASS) is a histone methyltransferase that includes the regulatory subunit Cfp1, which plays a key role in recognizing the methylation of histone H3 at lysine 4 (H3K4me3).
- - Research shows that while the yeast analog Spp1 has a specific structure for H3K4me3 recognition, metazoan Cfp1 lacks certain structural elements, leading to a unique binding configuration for H3K4me3.
- - Mutations in Cfp1 linked to cancer disrupt its ability to bind H3K4me3, suggesting these mutations may affect important epigenetic signaling pathways.
Article Abstract
Complex associating with SET1 (COMPASS) is a histone H3K4 tri-methyltransferase controlled by several regulatory subunits including CXXC zinc finger protein 1 (Cfp1). Prior studies established the structural underpinnings controlling H3K4me3 recognition by the PHD domain of Cfp1's yeast homolog (Spp1). However, metazoans Cfp1 lacks structural elements important for H3K4me3 stabilization in Spp1, suggesting that in metazoans, Cfp1 domain binds H3K4me3 differently. The structure of Cfp1 in complex with H3K4me3 shows unique features such as non-canonical coordination of the first zinc atom and a disulfide bond forcing the reorientation of Cfp1 N-terminus, thereby leading to an atypical H3K4me3 binding pocket. This configuration minimizes Cfp1 reliance on canonical residues important for histone binding functions of other PHD domains. Cancer-related mutations in Cfp1 impair H3K4me3 binding, implying a potential impact on epigenetic signaling. Our work highlights a potential diversification of PHD histone binding modes and the impact of cancer mutations on Cfp1 functions.
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| http://dx.doi.org/10.1016/j.str.2024.06.017 | DOI Listing |
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