Simultaneous single-cell proteomics and epigenetic analysis of histone deacetylase inhibition in human cells

Single-cell proteomics by mass spectrometry (SCP) is an emerging technology in which hundreds or thousands of proteins can be directly quantified in typical human cells. As the proteins detected and quantified by SCP are heavily biased toward proteins of highest abundance, chromatin proteins are an attractive target for analysis. To this end, I applied SCP to the analysis of cancer cells treated with mocetinostat, a class specific histone deacetylase inhibitor. I find that 16 PTMs can be confidently identified and localized with high site specificity in single cells. Drug treatment reveals apparent heterogeneity in the abundance and distribution of the accumulated acetylation sites in histone tails. While other techniques exist to measure histone modifications in single human cells, the approach presented here allows simultaneous quantification of hundreds of proteins, allowing phenotypic insight as well as epigenetic inferences in each individual cell. All raw and processed data described in this study has been made publicly available through the ProteomeXchange/MASSIVE repository system as MSV000093434.