Probing the acetylation code of histone H 4

Histone modifications play crucial roles in genome regulation with lysine acetylation being implicated in transcriptional control. Here we report a proteome‐wide investigation of the acetylation‐dependent protein–protein interactions of the N ‐terminal tail of histone H 4. Quantitative peptide‐based affinity MS experiments using the SILAC approach determined the interactomes of H 4 tails monoacetylated at the four known acetylation sites K 5, K 8, K 12, and K 16, bis‐acetylated at K 5/ K 12, triple‐acetylated at K 8/12/16 and fully tetra‐acetylated. A set of 29 proteins was found enriched on the fully acetylated H 4 tail while specific binders of the mono and bis‐acetylated tails were barely detectable. These observations are in good agreement with earlier reports indicating that the H 4 acetylation state establishes its regulatory effects in a cumulative manner rather than via site‐specific recruitment of regulatory proteins.