The development of an adult organism from a single fertilized egg is accompanied by the generation of some 300 different cell types. Each of these cell types expresses a specific subset
of genes in a highly regulated manner. During cellular differentiation, the genome in every cell
type remains unchanged, which raises one key question: How does a single genotype give rise to
such a large diversity of phenotypes? At least part of the answer to this question is epigenetics. Epigenetics is defined as changes in gene expression and phenotype that are independent of the underlying DNA sequence. In higher eukaryotes this is mainly achieved through methylation of
DNA on cytosines and by post-translational modifications of histones. These epigenetic modification patterns are dynamically being established, maintained and removed from the genome during differentiation and they help to create cell-type-specific gene expression profiles. Regulatory proteins can be recruited to these modifications and exert their function at the site of
recruitment. The specific binding of these so-called chromatin ‘readers’ therefore significantly contributes to the biological function of each individual epigenetic modification. Our lab is
using state-of-the-art quantitative mass-spectrometry based proteomics technology to identify chromatin readers for epigenetic histone and DNA modifications. We characterize the (dynamic) complexes that these readers form, we study their biology in (differentiated) stem cells and in different model organisms and we investigate their potential deregulation in cancer.
Current main projects
To decipher and functionally characterize the histone methyl lysine interactome (main publications: Vermeulen et al., Cell 2007; Vermeulen et al., Cell 2010; Bartke et al.,
Cell 2010; Eberl et al., Mol.Cell 2012)
To identify and functionally characterize interactions with methylcytosine and its oxidized derivatives during embryonic stem cell differentiation and in different model organisms (main publication: Spruijt et al., Cell 2013)
Purification, stoichiometry determination and functional characterization of protein complexes involved in chromatin structure and function (Vermeulen et al., Cell 2010; Smits et al., Nucleic Acids Res. 2013; van Nuland et al., Mol. Cell. Biol. 2013)
Figure: Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized derivatives
This figure shows a selection of identified ‘readers’ for methylcytosine (mC reader, top) and hydroxymethylcytosine (hmC reader, bottom) in mouse embryonic stem cells, neuronal
progenitor cells and adult mouse brain tissue. Interactions with methylcytosine and hydroxymethylcytosine are highly dynamic during development and show only a limited
For more information please refer to Spruijt et al., Cell. 2013 Feb 28;152(5):1146-59.