Advancing Epigenetics Towards Systems Biology

Stephen Cusack

Unit of Virus Host-Cell Interactions, European Molecular Biology Laboratory, Grenoble Outstation, Grenoble, France

Structure of Chromatin Modifying Machinery

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stephan cusack

We use X-ray crystallography as a central technique to obtain structural information on protein and protein-RNA complexes involved in RNA metabolism, translation, virus replication and epigenetics. Within epigenetics we focus on structural characterization of the Dosage Compensation (MSL) and Non-specific lethal (NSL) complexes. The MSL complex is a key player of the dosage compensation mechanism that balances expression levels of X-chromosomal genes between male and female. In Drosophila males it binds along the X-chromosome and acetylates H4 histones ultimately resulting in a two-fold up-regulation of most of the X-linked genes. The NSL complex is a newly identified major transcriptional regulator which also contains the histone acetyl-transferase MOF. We determine crystal structures of individual subunits or defined sub-complexes. The structural information is then used in in vitro and in vivo functional assays (in collaboration with the group of Dr. Asifa Akhtar) that help us understand how these large chromatin modifying machines function.

People involved:

  • Jan Kadlec (EMBL staff scientist)
  • Jorge Dias Do Nascimento (PhD student)

Latest publications

Structures of the inactive and active states of RIP2 kinase inform on the mechanism of activation.

28545134 - 2017-05-26
PLoS One 2017;12(5):e0177161

Pellegrini E, Signor L, Singh S, Boeri Erba E, Cusack S

Structural insights into reptarenavirus cap-snatching machinery.

28505175 - 2017-05-16
PLoS Pathog 2017 May 15;13(5):e1006400

Rosenthal M, Gogrefe N, Vogel D, Reguera J, Rauschenberger B, Cusack S, Günther S, Reindl S

Targeting Toxoplasma gondii CPSF3 as a new approach to control toxoplasmosis.

28148555 - 2017-02-06
EMBO Mol Med 2017 Mar;9(3):385-394

Palencia A, Bougdour A, Brenier-Pinchart MP, Touquet B, Bertini RL, Sensi C, Gay G, Vollaire J, Josserand V, Easom E, Freund YR, Pelloux H, Rosenthal PJ, Cusack S, Hakimi MA

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