Universiteit Leiden

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Chromatin organization & dynamics (Dr. Remus Dame)

Throughout all domains of life, from bacteria and archaea to eukaryotes, genomes adopt well-organized three-dimensional structures that can change in space and time to accommodate preferred transcriptional programs for environmental adaptation, the maintenance of cellular identity and differentiation trajectories. DNA folding is not only relevant to compact the genome and make it fit inside cells, it is also highly relevant for the functioning of the genome. Dynamic changes in genome architecture influence spatial and functional interactions in individual cells, to modulate gene expression patterns and accommodate cell fate changes during development and in response to environmental stimuli.

In our group we have three key objectives:

  1. unravel the structure of chromatin
  2. determine how the cellular environment affects chromatin structure
  3. determine how changes in chromatin structure drive changes in gene expression.

Our group investigates the structural and functional organization of genomes in bacteria and archaea. Different from the genome of eukaryotes, which is contained within a membrane-enclosed organelle, the nucleus, bacterial and archaeal genomes are not confined in a dedicated organelle. The folded genome of bacteria and archaea, referred to as the nucleoid, is structured by Nucleoid-Associated Proteins (NAPs). These proteins are functionally analogous to eukaryotic histones, but are generally unrelated in terms of sequence and structure. Our studies reveal that in bacteria and archaea, nucleoid-associated proteins organize and structure DNA by DNA bending, DNA bridging or nucleoprotein filament formation. Notably, many archaea (also) express true histone proteins, sequence homologs of eukaryotic histones. Unlike eukaryotic histones, these histones do not assemble on DNA into octameric nucleosomes, but into hypernucleosomes, which are variable in size, due to ‘unlimited’ side-by-side association of histone dimers. We investigate the functional implications of all these chromosomal protein-DNA complexes in terms of their roles in gene regulation. 

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