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Architecture of the Nucleosome Remodeling and Deacetylase (NuRD) Complex

Journal Article


Abstract


  • The Nucleosome Remodeling and Deacetylase (NuRD) complex is a ~1-MDa 10-subunit transcriptional co-regulator that plays essential roles in hematopoietic development, stem cell renewal and DNA repair, and is emerging as a central player in diseases ranging from cancer to thalassemia.

    Despite the importance of this complex, little is known about its structure and biochemical activity. Hence, knowledge of NuRD structure and function will provide broad insight into mechanisms of eukaryotic gene regulation.

    To address this deficit, we are using a barrage of biochemical and biophysical approaches. We recently showed that the NuRD complex can exist as a separate stable entity (without CHD4) dubbed the NuDe (Nucleosome Deacetylase) complex — disrupting the architectural paradigm that CHD4 is an integrated core component of the complex (1). In addition, a combination of mass spectrometry and single-particle electron microscopy has allowed us to piece together the architecture of NuRD through its subcomplexes at (quite) low resolution (2). Last but not least, we are now utilising single-molecule fluorescence to observe the remodeling activity of individual NuRD complexes in real time. This could reveal the biochemical mechanism by which this complex remodels chromatin during gene transcription and DNA repair.

Authors


  •   Low, Jason (external author)
  •   Silva, Ana P. G. (external author)
  •   Sharifitabar, Medhi (external author)
  •   Torrado, Mario (external author)
  •   Schmidberger, Jason W. (external author)
  •   Webb, Sarah (external author)
  •   Saathoff, Hinnerk (external author)
  •   Parker, Benjamin (external author)
  •   Paudel, Bishnu
  •   van Oijen, Antoine M.
  •   Landsberg, Michael (external author)
  •   Shepherd, Nicholas E. (external author)
  •   Mackay, Joel (external author)

Publication Date


  • 2017

Citation


  • Low, J. K. K., Silva, A. P. G., Sharifitabar, M., Torrado, M., Schmidberger, J., Webb, S. R., Saathoff, H., Parker, B. L., Paudel, B., van Oijen, A., Landsberg, M. J., Shepherd, N. E. & Mackay, J. P. (2017). Architecture of the Nucleosome Remodeling and Deacetylase (NuRD) Complex. The FASEB Journal, 31 (1 Supplement), 594.3-1-594.3-1. Chicago, United States Experimental Biology Meeting 2017

Start Page


  • 594.3-1

End Page


  • 594.3-1

Volume


  • 31

Issue


  • 1 Supplement

Place Of Publication


  • United States

Abstract


  • The Nucleosome Remodeling and Deacetylase (NuRD) complex is a ~1-MDa 10-subunit transcriptional co-regulator that plays essential roles in hematopoietic development, stem cell renewal and DNA repair, and is emerging as a central player in diseases ranging from cancer to thalassemia.

    Despite the importance of this complex, little is known about its structure and biochemical activity. Hence, knowledge of NuRD structure and function will provide broad insight into mechanisms of eukaryotic gene regulation.

    To address this deficit, we are using a barrage of biochemical and biophysical approaches. We recently showed that the NuRD complex can exist as a separate stable entity (without CHD4) dubbed the NuDe (Nucleosome Deacetylase) complex — disrupting the architectural paradigm that CHD4 is an integrated core component of the complex (1). In addition, a combination of mass spectrometry and single-particle electron microscopy has allowed us to piece together the architecture of NuRD through its subcomplexes at (quite) low resolution (2). Last but not least, we are now utilising single-molecule fluorescence to observe the remodeling activity of individual NuRD complexes in real time. This could reveal the biochemical mechanism by which this complex remodels chromatin during gene transcription and DNA repair.

Authors


  •   Low, Jason (external author)
  •   Silva, Ana P. G. (external author)
  •   Sharifitabar, Medhi (external author)
  •   Torrado, Mario (external author)
  •   Schmidberger, Jason W. (external author)
  •   Webb, Sarah (external author)
  •   Saathoff, Hinnerk (external author)
  •   Parker, Benjamin (external author)
  •   Paudel, Bishnu
  •   van Oijen, Antoine M.
  •   Landsberg, Michael (external author)
  •   Shepherd, Nicholas E. (external author)
  •   Mackay, Joel (external author)

Publication Date


  • 2017

Citation


  • Low, J. K. K., Silva, A. P. G., Sharifitabar, M., Torrado, M., Schmidberger, J., Webb, S. R., Saathoff, H., Parker, B. L., Paudel, B., van Oijen, A., Landsberg, M. J., Shepherd, N. E. & Mackay, J. P. (2017). Architecture of the Nucleosome Remodeling and Deacetylase (NuRD) Complex. The FASEB Journal, 31 (1 Supplement), 594.3-1-594.3-1. Chicago, United States Experimental Biology Meeting 2017

Start Page


  • 594.3-1

End Page


  • 594.3-1

Volume


  • 31

Issue


  • 1 Supplement

Place Of Publication


  • United States