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How are Centromeres Established? Chromatin and Neo-Centromere Seeding in Plants
Secondary Supervisor(s): Professor Jose Gutierrez-Marcos
University of Registration: University of Warwick
BBSRC Research Themes:
Project Outline
Every time a cell divides, its chromosomes must be accurately separated to ensure the new cells inherit the full set of genetic information. The "anchor points" that allow chromosomes to attach to the division machinery are called centromeres - which load a specialised multiprotein complex called the kinetochore. The functional centromere is specified epigenetically through incorporation of a centromere-specific histone variant (CENH3). Where a centromere forms on a chromosome influences key biological processes, such as suppressing meiotic recombination, which can shape the genetic potential available for crop breeding.
Despite their essential function centromere locations can migrate to new regions on a chromosome, but the mechanism by which this occurs is unclear. In Arabidopsis, only certain parts of the repetitive centromeric DNA are "active" (loaded with CENH3), while neighbouring repeats remain "silent". This multidisciplinary project will explore what distinguishes these "active" sites within the centromere, how chromatin states define centromere stability, and use engineering biology approaches to seed the active centromere at new genomic locations.
Objectives
1) Nanopore long-read sequencing and epigenomic profiling to map chromatin modifications across centromere regions.
2) Proteomics and mutant analysis to identify factors that stabilise active centromere sites.
3) Engineering biology approaches (CRISPR-based tethering systems such as SunTag) to artificially recruit CENH3 and regulators to new genomic loci, to seed functional neo-centromeres.
This exciting project will give you training in genetics, genomics, and engineering biology, and will address fundamental questions in chromosome biology with long-term potential for engineering plant centromeres for use in crops.
References
Naish M, et al., (2021) Science. 374:eabi7489.
Naish, M. (2024), New Phytol, 244: 2143-2149. https://doi.org/10.1111/nph.20149