show Abstracthide AbstractProfiling of the proteome bound to the chromatin in a simple, direct and reliable manner might result key to uncover the role of unpredicted chromatin factors in physiology and disease. We have developed a biochemical strategy named iChrock to capture the chromatin in a single purification step that provides a global view of the cellular chromatome and enables the identification of chromatin-bound proteins de novo. Integrating iChrock with genomic and functional data, we have unveiled the unexpected chromatin function of Adenosylhomocysteinase (AHCY), a major one-carbon pathway metabolic enzyme, in gene activation. Our study reveals a new regulatory axis between the metabolic state of pluripotent cells, ribosomal protein production and cell division during early phase of embryo development, by favoring the metabolic flux of methylation reactions in a local milieu. Overall design: List of ChIPseq and RNAseq samples (Wt and Ahcy mutant).