The deposition and removal of epigenetic marks is often controlled by large, multi-protein complexes. However, the molecular mechanisms underlying the activity of these complexes are in general not well understood.
The Nucleosome Remodeling and Deacetylase (NuRD) complex is one such epigenetic regulator. NuRD is conserved across all complex organisms and is essential for normal development. Recent data also suggest that components of the complex play important roles in both the DNA damage response and age-related memory loss. Despite being described 15 years ago, almost nothing is known about the architecture of the intact complex or how it actually alters chromatin structure.
We are using a range of biochemical and structural approaches, including x-ray crystallography, NMR spectroscopy, mass spectrometry and electron microscopy, in an effort to determine the structure and biochemical mechanism of action of NuRD. Our data provide a glimpse into the mechanisms through which complex coregulator complexes are recruited to target genes and help to map out the molecular events that drive gene regulation.