The presence of 5-methylcytosine (5mC) at gene promoters suppresses transcription, but the molecular mechanisms leading to derepression through active, site-specific DNA demethylation are poorly understood. The DNA damage–associated protein Gadd45a was previously suggested to participate in selective demethylation at the promoters of target genes through recruitment of the DNA repair machinery, but how it was targeted to specific sites remained unknown. Schäfer et al. now implicate the tumor suppressor Ing1—which contains a PHD finger domain that specifically binds H3K4me3—in DNA demethylation by recruiting Gadd45a to H3K4me3 sites. Ing1 and Gadd45a were found to interact, and cotransfection of Ing1 greatly stimulated the ability of Gadd45a to demethylate and reactivate the promoters of a reporter gene and the endogenous Mageb2 target gene. The stimulatory activity of Ing1 was dependent on an intact PHD domain, and reducing the level of H3K4me3 by knocking down Wrd5—a component of the MLL methyl-transferase complex—prevented the recruitment of Gadd45a and Ing1, increased 5mC levels at the promoter and impaired the induction of Mageb2 transcription. Finally, genome-wide changes in gene expression induced by the transfection of Gadd45a and Ing1 depended on the presence of H3K4me3 and correlated with reduced levels of DNA methylation at the promoters of target genes. These observations demonstrate that histone methylation can dynamically direct site-specific DNA demethylation and promote gene expression by recruiting specific histone readers, which in turn serve as adaptors for the demethylation machinery. (Genes Dev. 27, 261–273, 2013)