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Regulation of gene expression and cell fate by DNA (hydroxy)methylation

Objective

(Hydroxy)methylation of cytosine residues in eukaryotic DNA represents a major means to regulate gene expression during development. These modifications are considered to be epigenetic marks, since they have a profound impact on phenotype, but are inherited from mother to daughter cells independent of the underlying DNA sequence. Large efforts are currently underway to profile genome-wide DNA (hydroxy)methylation patterns in model organisms and in clinical studies, since aberrant DNA (hydroxy)methylation is a hallmark of cancer. Strikingly, the molecular mechanisms underlying the link between DNA (hydroxy)methylation and gene expression remain elusive. Although causal links are thought to arise from differential recruitment of transcription factors to (hydroxy)methylated DNA in a regulated manner during development, technical limitations have thus far prevented unbiased interaction screenings to investigate this hypothesis in detail. By using a unique combination of state-of-the-art quantitative mass spectrometry-based proteomics technology, genomics approaches and biochemical experiments, I will systematically investigate which proteins interact with or are repelled by (hydroxy)methylated DNA during stem cell differentiation into a neuronal lineage. Furthermore, I will investigate whether and to what extent these interactions regulate gene expression programs and lineage commitment. The results of these studies will reveal the mechanisms through which dynamic DNA (hydroxy)methylation patterns dictate cellular responses. This is anticipated to significantly increase our understanding of eukaryotic development and the role of epigenetics herein. Furthermore, these studies will pave the way for designing strategies aimed at interfering with altered epigenetics patterns in disease.

Call for proposal

ERC-2012-StG_20111109
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Host institution

STICHTING RADBOUD UNIVERSITEIT
Address
Houtlaan 4
6525 XZ Nijmegen
Netherlands

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Activity type
Higher or Secondary Education Establishments
Principal investigator
Michiel Vermeulen (Dr.)
Administrative Contact
Marion Bussemakers (Dr.)
EU contribution
€ 1 499 776

Beneficiaries (2)

STICHTING RADBOUD UNIVERSITEIT
Netherlands
EU contribution
€ 1 499 776
Address
Houtlaan 4
6525 XZ Nijmegen

See on map

Activity type
Higher or Secondary Education Establishments
Principal investigator
Michiel Vermeulen (Dr.)
Administrative Contact
Marion Bussemakers (Dr.)
UNIVERSITAIR MEDISCH CENTRUM UTRECHT

Participation ended

Netherlands
Address
Heidelberglaan 100
3584 CX Utrecht
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Joost Warsanis (Mr.)