Robert Illingworth

- Centre for Regenerative Medicine
Contact details
- Tel: 0131 651 9500 (Reception)
- Email: Robert.Illingworth@ed.ac.uk
Address
- Street
-
Centre for Regenerative Medicine,
Institute for Regeneration and Repair,
The University of Edinburgh,
Edinburgh BioQuarter,
5 Little France Drive, - City
- Edinburgh
- Post code
- EH16 4UU
Background
- 2019 – present. Group Leader. MRC Centre for Regenerative Medicine, University of Edinburgh.
- 2018–2019. Simons Initiative for the Developing Brain (SIDB) Transition to independence post. The University of Edinburgh.
- 2010–2018. Postdoc with Prof. Wendy Bickmore. MRC Human Genetics Unit. Epigenetics of mammalian embryonic development.
- 2008-2010. Postdoc with Sir Adrian Bird. Wellcome Trust Centre for Cell Biology, The University of Edinburgh. DNA methylation screening in primary Human brain tissue.
- 2004-2008. PhD student with Sir Adrian Bird. Wellcome Trust Centre for Cell Biology, The University of Edinburgh. Developing novel biochemical approaches for the characterisation of mammalian CpG island methylation.
- 1999-2003. BSc in Molecular Biology. The University of Edinburgh.
Research summary
Epigenetics and Brain Development
Mammalian embryonic development is the process whereby a single naïve cell is expanded, and serially specialised, to produce all of the functional cell types of the adult body. This intricate process is governed by proteins, which bind to regulatory DNA sequences and establish the appropriate gene expression over time and in the correct locations. One such family of protein effectors called polycomb repressive complexes (PRCs), function to block gene expression by chemically and physically modifying chromatin - the packaged form of DNA.
The aim of my research is to understand how these epigenetic regulators control gene expression during early brain development. In particular I am interested in how histone-modifying enzymes control the balance between self-renewal and differentiation to ensure appropriate brain growth. Understanding this balance is key to interpreting the molecular differences seen in a broad-range of neurodevelopmental disorders (NDDs).
Aims and areas of interest
Building a brain, the most compositionally and functionally complex human organ, requires the tightly coordinated expansion, specialization and migration of neural cell types. Transcription factors govern this process, however the spatial and temporal fidelity which is essential for brain function relies heavily on epigenetic modifiers. By altering the chemical and structural properties of chromatin, epigenetic systems ensure the proportionate transcriptional response to developmental cues. Accordingly, causal mutations in epigenetic regulators are prominent in both congenital and acquired brain disorders. Often the phenotypes and underlying genetic lesions of NDDs are known, yet the precise molecular aetiology is not. This is due to our limited understanding of how epigenetic systems drive gene expression programmes during normal brain development.
We combine cutting edge molecular techniques in combination with mouse and cell based model systems to understand the role played by epigenetic modifiers during brain development, and how their mutation contributes to disease.
Specific Aims:
- How are epigenetic modifiers targeted to chromatin in the developing brain?
- How do neural-specific protein components adapt the functionality of epigenetic modifiers?
- What is the relative contribution of histone modification activity for gene regulation in the neural lineage?
- Why do mutations in functionally opposing epigenetic regulators lead to equivalent disordered brain phenotypes?
-
RINGs, DUBs and Abnormal Brain Growth—Histone H2A Ubiquitination in Brain Development and Disease
In:
Epigenomes, vol. 6
DOI: https://doi.org/10.3390/epigenomes6040042
Research output: Contribution to Journal › Article (Published) -
PRL3-DDX21 transcriptional control of endolysosomal genes restricts melanocyte stem cell differentiation
(16 pages)
In:
Developmental Cell, vol. 54, pp. 317-332.E9
DOI: https://doi.org/10.1016/j.devcel.2020.06.013
Research output: Contribution to Journal › Article (Published) -
A Central Role for Canonical PRC1 in Shaping the 3D Nuclear Landscape
In:
Genes and Development, vol. 34, pp. 931-949
DOI: https://doi.org/10.1101/gad.336487.120
Research output: Contribution to Journal › Article (Published) -
Coolpup.py: versatile pile-up analysis of Hi-C data
In:
Bioinformatics
DOI: https://doi.org/10.1093/bioinformatics/btaa073
Research output: Contribution to Journal › Article (E-pub ahead of print) -
DNA Methylation Directs Polycomb-Dependent 3D Genome Re-organization in Naive Pluripotency
(18 pages)
In:
Cell Reports, vol. 29, pp. 1974-1985.e6
DOI: https://doi.org/10.1016/j.celrep.2019.10.031
Research output: Contribution to Journal › Article (Published) -
Decreased enhancer-promoter proximity accompanying enhancer activation
(19 pages)
In:
Molecular Cell, vol. 76, pp. 473-484.e7
DOI: https://doi.org/10.1016/j.molcel.2019.07.038
Research output: Contribution to Journal › Article (Published) -
Chromatin Folding and Nuclear Architecture: PRC1 Function in 3D
In:
Current Opinion in Genetics and Development
DOI: https://doi.org/10.1016/j.gde.2019.06.006
Research output: Contribution to Journal › Article (Published) -
Polycomb enables primitive endoderm lineage priming in embryonic stem cells
In:
eLIFE, vol. 5
DOI: https://doi.org/10.7554/eLife.14926
Research output: Contribution to Journal › Article (Published) -
Loss of Tet1 associated 5-hydroxymethylcytosine is concomitant with aberrant promoter hypermethylation in liver cancer
In:
Cancer Research
DOI: https://doi.org/10.1158/0008-5472.CAN-15-1910
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Polycomb-mediated chromatin compaction weathers the STORM
In:
Genome Biology, vol. 17, pp. 35
DOI: https://doi.org/10.1186/s13059-016-0899-y
Research output: Contribution to Journal › Article (Published) -
The E3 ubiquitin ligase activity of Ring1B is not essential for early mouse development
(6 pages)
In:
Genes and Development, vol. 29, pp. 1897-1902
DOI: https://doi.org/10.1101/gad.268151.115
Research output: Contribution to Journal › Article (Published) -
Inter-individual variability contrasts with regional homogeneity in the human brain DNA methylome
(13 pages)
In:
Nucleic Acids Research, vol. 43, pp. 732-744
DOI: https://doi.org/10.1093/nar/gku1305
Research output: Contribution to Journal › Article (Published) -
Spatial genome organization: contrasting views from chromosome conformation capture and fluorescence in situ hybridization
(14 pages)
In:
Genes and Development, vol. 28, pp. 2778-2791
DOI: https://doi.org/10.1101/gad.251694.114
Research output: Contribution to Journal › Article (Published) -
Chromatin decondensation is sufficient to alter nuclear organization in embryonic stem cells
(5 pages)
In:
Science, vol. 346, pp. 1238-1242
DOI: https://doi.org/10.1126/science.1259587
Research output: Contribution to Journal › Article (Published) -
Cfp1 integrates both CpG content and gene activity for accurate H3K4me3 deposition in embryonic stem cells
(15 pages)
In:
Genes and Development, vol. 26, pp. 1714-1728
DOI: https://doi.org/10.1101/gad.194209.112
Research output: Contribution to Journal › Article (Published) -
PRC1 and PRC2 Are Not Required for Targeting of H2A.Z to Developmental Genes in Embryonic Stem Cells
(13 pages)
In:
PLoS ONE, vol. 7
DOI: https://doi.org/10.1371/journal.pone.0034848
Research output: Contribution to Journal › Article (Published) -
CpG islands influence chromatin structure via the CpG-binding protein Cfp1
(5 pages)
In:
Nature, vol. 464, pp. 1082-1086
DOI: https://doi.org/10.1038/nature08924
Research output: Contribution to Journal › Article (Published) -
The role of MeCP2 in the brain
(1 page)
In:
The FEBS Journal, vol. 276, pp. 5-5
Research output: Contribution to Journal › Meeting abstract (Published) -
CpG islands -'a rough guide'
(8 pages)
In:
FEBS Letters, vol. 583, pp. 1713-20
DOI: https://doi.org/10.1016/j.febslet.2009.04.012
Research output: Contribution to Journal › Article (Published)
- Dr Ian Adam, MRC HGU, Edinburgh.
- Prof Steve Pollard, MRC CRM, Edinburgh.
- Dr Tilo Kunath, MRC CRM, Edinburgh.
- Prof Josh Brickman, Center for Stem Cell Research and Developmental Biology (Danstem), Copenhagen.