Research Group VERMEULEN

Faculty of Medicine, University Medical Centre Utrecht, Dept. Molecular Cancer Research
Contact: Dr. Michiel Vermeulen
E-mail: M.Vermeulen-3@umcutrecht.nl
Website: http://groups.mcr.umcutrecht.nl/vermeulen/

General research focus: Quantitative proteomics and chromatin biology

In a eukaryotic nucleus, DNA is packed in a structural polymer called chromatin. Chromatin serves to store genetic material, but also plays an active role in regulating processes such as DNA repair, replication and transcription. The nucleosome, an octamer of four different histone proteins around which the DNA is wrapped, represents the basic repeating unit within chromatin. Nucleosomes pose a barrier for reading the stored DNA-sequence information. Recently, a large number of transcription factors have been identified and characterized that are able to alter the structure of chromatin and by doing so are able to regulate the accessibility and transcriptional activity of genes. Of particular interest are proteins and protein complexes that post-translationally modify histones (so-called chromatin "writers"). These modifications include acetylation, phosphorylation, methylation and ubiquitination which are thought to provide an epigenetic "barcode" that partly determines the expression status of individual genes or chromosomal loci.

Emerging evidence causally links epigenetic alterations of chromatin to a disturbed proliferation - differentiation balance implicated in many diseases, including cancer. Chromatin regulators are therefore seen as promising targets for the development of therapeutic drugs. To gain insights into the physiological and pathological versions of these enzymes it is not only essential to determine their genomic targets but also to decipher their downstream effects. One of these effects is thought to be the recruitment or stabilization of protein complexes that subsequently can exert their function at the site of recruitment.

We apply high-accuracy quantitative mass spectrometry to study chromatin structure and function in general and histone modifications in particular. Our long term goal is to understand the mechanisms via which histone modifications contribute to regulate processes in the nucleus such as transcription and DNA repair. Our current main interests are:



  • To decipher and functionally characterize the histone code interactome using a SILAC-based peptide pull-down approach (see figure).

  • The identification and functional characterization of novel protein complexes involved in chromatin structure and function.

  • Establishment of technology that allows the identification and quantitation of proteins that are brought down in chromatin immunoprecipitation (ChIP) experiments.


Mass spectrometry-based quantitative proteomics forms the basis of many of our experiments. We have access to an LTQ-Orbitrap mass spectrometer and make use of software developed in the lab of Matthias Mann (MaxQuant) to analyze our data. In addition, we apply classic biochemical techniques such as recombinant protein expression and purification, protein tagging in mammalian cells and functional knock-down approaches.



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