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Harris Group: Readers of the ‘histone code’: the missing link in triggering gene activity

UF / OTHER

Supervisor: Jake Harris (Plant Sciences)

Project summary:

Regulating access to DNA is a primary means by which gene expression states are controlled. Epigenetic marks can directly influence transcription by affecting DNA accessibility, and by serving as molecular signposts for 'reader' proteins that can recruit transcriptional machinery. Over the past 20 years, we have learned where these marks are in the genome, but our understanding of how these marks are read and perceived by the cell lags far behind. Identifying these reader proteins is an essential step in understanding the links between particular epigenetic states and their functions. The first stage of this project will be to identify the readers of key histone marks. The work will involve a quantitative proteomics based 'molecular fishing' approach - performed in collaboration with world experts in Germany. In the second phase of the work, readers proteins will be assessed using genomics (ChIP-seq/Cut&Tag and RNA-seq), transcriptional reporter assays, and biochemical approaches, to gain a mechanistic understanding of the role and function of key histone reader proteins.

The student will gain expertise in a range standard molecular biology techniques, as well as advanced genomics (generating high throughput sequencing libraries) and bioinformatic approaches. In addition, the student will gain exposure to an international collaboration.

References:

  • Xiao J, Lee US, Wagner D. (2016). Tug of war: adding and removing histone lysine methylation in Arabidopsis. Curr Opin Plant Biol. Dec;34:41-53. https://doi:10.1016/j.pbi.2016.08.002
  • Musselman, C. A., Lalonde, M. E., Côté, J., & Kutateladze, T. G. (2012). Perceiving the epigenetic landscape through histone readers. Nature structural & molecular biology, 19(12), 1218–1227. https://doi.org/10.1038/nsmb.2436
  • Harris CJ, Scheibe M, Wongpalee SP, Liu W, Cornett EM, Vaughan RM, Li X, Chen W, Xue Y, Zhong Z, Yen L, Barshop WD, Rayatpisheh S, Gallego-Bartolome J, Groth M, Wang Z, Wohlschlegel JA, Du J, Rothbart SB, Butter F, Jacobsen SE. (2018). A DNA methylation reader complex that enhances gene transcription. Science. Dec 7;362(6419):1182-1186. doi: 10.1126/science.aar7854. PMID: 30523112; PMCID: PMC6353633.

   

 

 

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