Chromatin, composed of DNA and histones forming a nucleosomal repeating unit, is the heritable substrate of many biological processes, such as gene regulation, mitosis, DNA repair and apoptosis. Many different mechanisms exist to change the structure of the chromatin, thereby influencing the functional output. These processes include the methylation of the DNA itself, post-translational histone modifications (PTMs), remodeling of nucleosomes and the incorporation of specialized histone variants. Our goals are to understand the biology of mammalian histone variants and their deposition machineries. Further, we try to decipher how mutations and deregulation of these protein networks affect normal cell functions leading to diseases, most notably cancer.