New technology developed in the Ruthenburg lab exposes widely held assumptions about antibody specificity and the practices of Chromatin Immunoprecipitation (ChIP) to be highly flawed. A recent Molecular Cell study led by undergraduate Rohan Shah and CMB graduate student Adrian Grzybowski, discovered that conventional methods for “validating antibodies” for use in ChIP display poor specificity. As a consequence, this study reveals that many literature H3K4 methylation paradigms are flawed due to problematic antibodies or other pitfalls in conventional methods. Yet using this sensitive quantitative method, new direct connections between enhancer-borne histone marks and the transcriptional output of their target promoters are revealed. Yet the sensitive quantitative method developed to improve ChIP with internal standard calibration, coupled with high-quality antibodies can discern new direct connections between enhancer-borne histone marks and the transcriptional output of their target promoters are revealed.