The ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression. This study identifies the PHD domain of the ING family of tumor suppressor proteins as a novel class of methylated H3K4 effector domains. The ING2 PHD domain specifically and robustly binds to H3K4me3 and H3K4me2. ING2, a subunit of the repressive mSin3a–HDAC1 complex, binds with high affinity to H3K4me3. In response to DNA damage, the ING2 PHD domain stabilizes the mSin3a–HDAC1 complex at the promoters of proliferation genes, promoting gene repression. ING2 modulates cellular responses to genotoxic insults, and these functions depend on its interaction with H3K4me3. The study shows that H3K4 trimethylation is critical for ING2 PHD domain binding to histone H3 at chromatin in vitro. The ING2 PHD domain also binds to H3K4me3 in physiological chromatin in cells, and its recognition of H3K4me3 is essential for ING2 function in DNA damage responses. The PHD domain of ING2 is a dual-specificity module that binds both PtdIns(5)P and H3K4me3. These activities are separable by specific mutations within the domain, and both are critical for ING2 cellular functions. The study highlights the role of chromatin modifications in gene regulation, showing that the recognition of chromatin modifications by effector proteins, rather than the specific modification per se, determines biological function. The findings suggest that H3K4 methylation is pivotal for gene repression and may be involved in tumor suppressor mechanisms. The ING2 PHD domain is necessary and sufficient for ING2 interaction with H3K4me3 in vitro. The study also shows that the ING2 PHD domain is required for the association of ING2 with H3K4me3 at chromatin in vivo. The ING2 PHD domain recognition of H3K4me3 is critical for ING2 function in the cellular response to DNA damage. The study demonstrates that the PHD domain of ING2 is a novel class of binding modules for methylated H3K4. The findings suggest that the PHD domains of other ING proteins also bind methylated H3K4, and the PHD domain of the nucleosome remodelling factor (NURF) complex component BPTF also recognizes methylated H3K4, indicating a more general role for PHD domains as methyl-lysine effector domains. The study provides evidence that the recognition of chromatin modifications by effector proteins determines biological function, expanding the diversity of signaling at chromatin.The ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression. This study identifies the PHD domain of the ING family of tumor suppressor proteins as a novel class of methylated H3K4 effector domains. The ING2 PHD domain specifically and robustly binds to H3K4me3 and H3K4me2. ING2, a subunit of the repressive mSin3a–HDAC1 complex, binds with high affinity to H3K4me3. In response to DNA damage, the ING2 PHD domain stabilizes the mSin3a–HDAC1 complex at the promoters of proliferation genes, promoting gene repression. ING2 modulates cellular responses to genotoxic insults, and these functions depend on its interaction with H3K4me3. The study shows that H3K4 trimethylation is critical for ING2 PHD domain binding to histone H3 at chromatin in vitro. The ING2 PHD domain also binds to H3K4me3 in physiological chromatin in cells, and its recognition of H3K4me3 is essential for ING2 function in DNA damage responses. The PHD domain of ING2 is a dual-specificity module that binds both PtdIns(5)P and H3K4me3. These activities are separable by specific mutations within the domain, and both are critical for ING2 cellular functions. The study highlights the role of chromatin modifications in gene regulation, showing that the recognition of chromatin modifications by effector proteins, rather than the specific modification per se, determines biological function. The findings suggest that H3K4 methylation is pivotal for gene repression and may be involved in tumor suppressor mechanisms. The ING2 PHD domain is necessary and sufficient for ING2 interaction with H3K4me3 in vitro. The study also shows that the ING2 PHD domain is required for the association of ING2 with H3K4me3 at chromatin in vivo. The ING2 PHD domain recognition of H3K4me3 is critical for ING2 function in the cellular response to DNA damage. The study demonstrates that the PHD domain of ING2 is a novel class of binding modules for methylated H3K4. The findings suggest that the PHD domains of other ING proteins also bind methylated H3K4, and the PHD domain of the nucleosome remodelling factor (NURF) complex component BPTF also recognizes methylated H3K4, indicating a more general role for PHD domains as methyl-lysine effector domains. The study provides evidence that the recognition of chromatin modifications by effector proteins determines biological function, expanding the diversity of signaling at chromatin.