Histone modifications play key roles in the regulation of gene expression. In embryonic stem cells, promoters of developmental genes simultaneously carry histone H3 lysine 4 trimethylation (H3K4me3), which is usually found at active promoters, and H3K27me3, a hallmark of repressive chromatin. These so-called bivalent domains are thought to poise genes for timely induction during development, but it remains unclear whether bivalent domains are required for proper differentiation and if so, how their associated marks regulate gene expression. Moreover, it is unclear how poised enhancers communicate with, and mediate activation of, bivalent promoters. Our lab is employing biochemical, chromatin biology, and imaging approaches to address these questions.
We are seeking enthusiastic, talented, and creative students to join our group. The focus of the project will be chosen in dialogue with the student, combining interests of the student with current directions of the group. Potential areas include the establishment of bivalent domains, roles of nuclear organisation and bivalent binding proteins in bivalency-mediated poising, enhancer-promoter hierarchies in gene activation, and investigations into the potential mitotic bookmarking of bivalent domains.
This project will allow to gain extensive knowledge in biochemistry, chromatin biology, and epigenetics. It will provide training opportunities in CRISPR-based genome and epigenome editing, genome-wide approaches such as ChIP-seq and RNA-seq, as well as in the bioinformatics (in conjunction with the bioinformatics core at the Wellcome Centre for Cell Biology) involved in data analysis. Moreover, chemical biology, imaging, and mass spectrometry approaches can be applied as well.
Please visit the lab website for more information: http://www.wcb.ed.ac.uk/research/philipp-voigt
. A variety of funding sources are available, including for UK, EU, and international students. Informal enquiries should be made to Dr. Philipp Voigt: [email protected]
Voigt, P., Tee, W.-W., & Reinberg, D. (2013). A double take on bivalent promoters. Genes Dev 27, 1318-1338.
Voigt, P., LeRoy, G., Drury III, W. J., Zee, B. M., Son, J., Beck, D. B., Young, N. L., Garcia, B. A., & Reinberg, D. (2012). Asymmetrically Modified Nucleosomes. Cell 151, 181–193.