D'Arcy, Sheena

Permanent URI for this collectionhttps://hdl.handle.net/10735.1/5588

Sheena D'Arcy joined the UTD Chemistry faculty in 2015. Her research interests include:

  • Chromatin dynamics
  • Cell-specific gene expression
  • X-ray crystallography
  • Structural biology
  • hydrogen-deuterium exchange
  • mass spectroscopy
Her work has implications for cancer treatment and regenerative medicine.

ORCID page

Browse

Recent Submissions

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Characterization of Caenorhabditis elegans Nucleosome Assembly Protein 1 Uncovers the Role of Acidic Tails in Histone Binding
    (Amer Chemical Soc, 2018-12-06) Sarkar, Prithwijit; Zhang, Naifu; Bhattacharyya, Sudipta; Salvador, Karlah; D'Arcy, Sheena; 0000-0001-5055-988X (D'Arcy, S); Sarkar, Prithwijit; Zhang, Naifu; Salvador, Karlah; D'Arcy, Sheena
    Nucleosome assembly proteins (Naps) influence chromatin dynamics by directly binding to histones. Here we provide a comprehensive structural and biochemical analysis of a Nap protein from Caenorhabditis elegans (CeNap1). CeNap1 naturally lacks the acidic N-terminal tail and has a short C-terminal tail compared to many other Nap proteins. Comparison of CeNap1 with full length and tail-less constructs of Saccharomyces cerevisiae Nap1 uncovers the role of these tails in self-association, histone binding, and Nap competition with DNA for H2A-H2B. We find that the presence of tails influences the stoichiometry of H2A-H2B binding and is required to complete the interactions between H2A-H2B and DNA. The absolute stoichiometry of the Nap protein and H2A-H2B complex is 2:1 or 2:2, with only a very small population of higher-order oligomers occurring at 150 mM NaCl. We also show that H3-H4 binds differently than H2A-H2B and that an (H3-H4)(2) tetramer can simultaneously bind two Nap₂ protein homodimers.
  • Thumbnail Image
    Item
    Importin-9 Wraps Around the H2A-H2B Core to Act as Nuclear Importer and Histone Chaperone
    (NLM (Medline)) Padavannil, A.; Sarkar, Prithwijit; Kim, S. J.; Cagatay, T.; Jiou, J.; Brautigam, C. A.; Tomchick, D. R.; Sali, A.; D'Arcy, Sheena; Chook, Y. M.; 0000-0001-5055-988X (D'Arcy, S); Sarkar, Prithwijit; D'Arcy, Sheena
    We report the crystal structure of nuclear import receptor Importin-9 bound to its cargo, the histones H2A-H2B. Importin-9 wraps around the core, globular region of H2A-H2B to form an extensive interface. The nature of this interface coupled with quantitative analysis of deletion mutants of H2A-H2B suggests that the NLS-like sequences in the H2A-H2B tails play a minor role in import. Importin-9•H2A-H2B is reminiscent of interactions between histones and histone chaperones in that it precludes H2A-H2B interactions with DNA and H3-H4 as seen in the nucleosome. Like many histone chaperones, which prevent inappropriate non-nucleosomal interactions, Importin-9 also sequesters H2A-H2B from DNA. Importin-9 appears to act as a storage chaperone for H2A-H2B while escorting it to the nucleus. Surprisingly, RanGTP does not dissociate Importin-9•H2A-H2B but assembles into a RanGTP•Importin-9•H2A-H2B complex. The presence of Ran in the complex, however, modulates Imp9-H2A-H2B interactions to facilitate its dissociation by DNA and assembly into a nucleosome. © 2019 Padavannil et al.
  • Thumbnail Image
    Item
    Histone Chaperone Nap1 Is a Major Regulator of Histone H2A-H2B Dynamics at the Inducible Gal Locus
    (Amer Soc Microbiology, 2016-02-16) Chen, Xu; D'Arcy, Sheena; Radebaugh, Catherine A.; Krzizike, Daniel D.; Giebler, Holli A.; Huang, Liangquan; Nyborg, Jennifer K.; Luger, Karolin; Stargell, Laurie A.; D'Arcy, Sheena
    Histone chaperones, like nucleosome assembly protein 1 (Nap1), play a critical role in the maintenance of chromatin architecture. Here, we use the GAL locus in Saccharomyces cerevisiae to investigate the influence of Nap1 on chromatin structure and histone dynamics during distinct transcriptional states. When the GAL locus is not expressed, cells lacking Nap1 show an accumulation of histone H2A-H2B but not histone H3-H4 at this locus. Excess H2A-H2B interacts with the linker DNA between nucleosomes, and the interaction is independent of the inherent DNA-binding affinity of H2A-H2B for these particular sequences as measured in vitro. When the GAL locus is transcribed, excess H2A-H2B is reversed, and levels of all chromatinbound histones are depleted in cells lacking Nap1. We developed an in vivo system to measure histone exchange at the GAL locus and observed considerable variability in the rate of exchange across the locus in wild-type cells. We recapitulate this variability with in vitro nucleosome reconstitutions, which suggests a contribution of DNA sequence to histone dynamics. We also find that Nap1 is required for transcription-dependent H2A-H2B exchange. Altogether, these results indicate that Nap1 is essential for maintaining proper chromatin composition and modulating the exchange of H2A-H2B in vivo.

Works in Treasures @ UT Dallas are made available exclusively for educational purposes such as research or instruction. Literary rights, including copyright for published works held by the creator(s) or their heirs, or other third parties may apply. All rights are reserved unless otherwise indicated by the copyright owner(s).