The development of an adult human being from a single fertilized egg is accompanied by the generation of ~200 functionally distinct cell types. Each of these cell types expresses only a subset of the 20.000 genes that the human genome encodes for. Cell-type specific gene expression patterns thus ensure the generation of hundreds of phenotypes based on a single genotype. Transcription factors play an important role in driving cell-type specific gene expression, but so-called epigenetic modifications of DNA and core histones also regulate changes in gene expression and phenotype during development and during adult life. Our lab is using state-of-the-art quantitative mass-spectrometry based (interaction) proteomics and next generation DNA sequencing technology to decipher (epi)genetic regulation of gene expression in (differentiated) stem cells and cancer cells.