About the Project
Histone modifications play key roles in the regulation of gene expression. In embryonic stem cells, promoters of developmental genes carry a signature combination of 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 how bivalent domains and their associated marks regulate gene expression. In addition to the two defining methylation marks, additional modifications are present at bivalent domains as well, but have received much less attention.
Recent findings indicate that the histone acetyltransferase MORF is present at developmental genes in both Drosophila and mammals. MORF and its acetylation marks thus represent promising candidates for factors that contribute to either establishment or resolution of bivalency in embryonic stem cells. In this project, we will determine the role of MORF and its acetylation mark by generating knockout as well as knockin cell lines using CRISPR. Differentiation assays will be performed to analyse how absence of the complex or its mark is affecting resolution of bivalent chromatin. Using mutational studies, we will address how MORF is recruited to bivalent promoters. We will further generate recombinant chromatin carrying the marks placed by MORF to identify binding proteins for these as yet poorly understood acetylation marks. These approaches will be combined with a systematic analysis of available ChIPseq data to generate an exhaustive overview of marks co-occurring at bivalent domains in order to identify further factors that are involved in their regulation and thus stem cell differentiation.
This project will allow to gain extensive knowledge in chromatin biology and epigenetics. It will provide training opportunities in genome-wide approaches such as ChIP-seq and RNA-seq, as well as in the bioinformatics involved in data analysis. Moreover, biochemical and mass spectrometry approaches will be employed 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 Address Removed].
Funding Notes
The “Apply online” button on this page will take you to our Online Application checklist. Please complete each step and download the checklist which will provide a list of funding options and guide you through the application process.
If you would like us to consider you for one of our scholarships you must apply by 12 noon on 13 December 2018 at the latest.
References
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.
Kang, H., Jung, Y.L., McElroy, K.A., Zee, B.M., Wallace, H.A., Woolnough, J.L., Park P.J., & Kuroda M.I. (2017). Bivalent complexes of PRC1 with orthologs of BRD4 and MOZ/MORF target developmental genes in Drosophila. Genes Dev. 31, 1988–2002.
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