Dr Simon Whitehall
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- Telephone: +44 (0) 191 208 5989
- Fax: +44 (0) 191 208 7424
- Address: Institute for Cell and Molecular Biosciences
The Medical School
University of Newcastle upon Tyne
Newcastle upon Tyne
Epigenetic Control of Gene Expression and Genome Integrity
My laboratory studies how the modulation of chromatin is used by eukaryotic cells to regulate fundamental processes such as gene expression and genome stability.
PhD VACANCIES - we are always open to informal enquiries from prospective PhD students, whether Home/EU or non-EU. Please feel free to email me if you are interested (firstname.lastname@example.org).
1989-1992 PhD, Gatsby Charitable Foundation Studentship, University of Sussex
During my PhD I studied bacterial transcription in Prof Ray Dixon’s laboratory. My research centred upon the role of DNA topology in control of transcription initiation from σ54-dependent promoters.
1993-1996 HFSPO Post-Doctoral Research Fellow, University of California San Diego, La Jolla USA
During my first post-doctoral position in Dr Peter Geiduschek’s laboratory I studied the enzymology of RNA polymerase III. I identified a backtracking activity in RNA polymerase III and also studied the assembly of transcription factors at the U6 promoter.
1996-1999 Post-Doctoral Research Fellow, Cancer Research UK, London Research Institute
My second post-doctoral position was in Prof Nic Jones’ laboratory and focussed upon the control of cell cycle-dependent transcription. Here my research utilised the fission yeast, Schizosaccharomyces pombe as a model system.
Epigenetic Control of Gene Expression and Genome Integrity
The human genome is made up of nearly two metres of DNA that must be compacted into a nucleus of just a few microns in diameter. This is achieved by packaging DNA with histone proteins into a complex called chromatin. Importantly, the modulation of chromatin structure is a key mechanism for regulating the function of the underlying DNA and as such, chromatin represents a fundamental layer of epigenetic control. Indeed, defects in chromatin are associated with gene dysregulation, genome instability and a number of diseases states that include cancers and neurodegenerative disorders.
We primarily focus on the role of histone chaperones that control the assembly and disassembly chromatin. We also study how chromatin is employed to keep control of mobile genetic elements and so maintain genome integrity. Our experiments predominantly utilise the fission yeast, Schizosaccharomyces pombe which is very easy to manipulate genetically. As the processes and proteins that we study have been highly conserved throughout evolution, our fission yeast studies provide insight into how the function of chromatin is controlled in humans and how aberrant chromatin structure results in disease states.
- Murton HE, Grady PJR, Chan TH, Cam HP, Whitehall SK. Restriction of retrotransposon mobilization in Schizosaccharomyces pombe by transcriptional silencing and higher-order chromatin organization. Genetics 2016, 203(3).
- Gal C, Murton HE, Subramanian L, Whale AJ, Moore KM, Paszkiewicz K, Codlin S, Bähler J, Creamer KM, Partridge JF, Allshire RC, Kent NA, Whitehall SK. Abo1, a conserved bromodomain AAA-ATPase, maintains global nucleosome occupancy and organisation. EMBO Reports 2016, 17(1), 79-93.
- Narayanan S, Dubarry M, Lawless C, Banks AP, Wilkinson DJ, Whitehall SK, Lydall D. Quantitative Fitness Analysis Identifies exo1∆ and Other Suppressors or Enhancers of Telomere Defects in Schizosaccharomyces pombe. PloS ONE 2015, 10(7), e0132240.
- Gal C, Moore KM, Paszkiewicz K, Kent NA, Whitehall SK. The impact of the HIRA histone chaperone upon global nucleosome architecture. Cell Cycle 2015, 14(1), 123-134.
- Pai CC, Deegan RS, Subramanian L, Gal C, Sarkar S, Blaikley EJ, Walker C, Hulme L, Bernhard E, Codlin S, Bähler J, Allshire R, Whitehall S, Humphrey TC. A histone H3K36 chromatin switch coordinates DNA double-strand break repair pathway choice. Nature Communications 2014, 5, 4091.
- Flanagan MD, Whitehall SK, Morgan BA. An Atg10-like E2 enzyme is essential for cell cycle progression but not autophagy in Schizosaccharomyces pombe. Cell Cycle 2013, 12(2), 271-277.
- Purtill FS, Whitehall SK, Williams ES, McInerny CJ, Sharrocks AD, Morgan BA. A homeodomain transcription factor regulates the DNA replication checkpoint in yeast. Cell Cycle 2011, 10(4), 664-670.
- Anderson HE, Kagansky A, Wardle J, Rappsilber J, Allshire RC, Whitehall SK. Silencing Mediated by the Schizosaccharomyces pombe HIRA Complex Is Dependent upon the Hpc2-Like Protein, Hip4. PLoS One 2010, 5(10), e13488.
- Anderson HE, Wardle J, Korkut SV, Murton HE, López-Maury L, Bähler J, Whitehall SK. The Fission Yeast HIRA Histone Chaperone Is Required for Promoter Silencing and the Suppression of Cryptic Antisense Transcripts. Molecular and Cellular Biology 2009, 29(18), 5158-5167.
- McFarlane RJ, Whitehall SK. tRNA genes in eukaryotic genome organization and reorganization. Cell Cycle 2009, 8(19), 3102-3106.
- Dainty SJ, Kennedy CA, Watt S, Bähler J, Whitehall SK. Response of Schizosaccharomyces pombe to Zinc Deficiency. Eukaryotic Cell 2008, 7(3), 454-464.
- Greenall A, Williams ES, Martin KA, Palmer JM, Gray J, Liu C, Whitehall SK. Hip3 interacts with the HIRA proteins Hip1 and Slm9 and is required for transcriptional silencing and accurate chromosome segregation. Journal of Biological Chemistry 2006, 281(13), 8732-8739.
- Lydall DA, Whitehall SK. Chromatin and the DNA damage response. DNA Repair 2005, 4(10), 1195-1207.
- Blackwell C, Martin KA, Greenall A, Pidoux A, Allshire RC, Whitehall SK. The Schizosaccharomyces pombe HIRA-like protein hip1 is required for the periodic expression of histone genes and contributes to the function of complex centromeres. Molecular and Cellular Biology 2004, 24(10), 4309-4320.
- Bulmer R, Pic-Taylor A, Whitehall SK, Martin KA, Millar JBA, Quinn J, Morgan BA. The forkhead transcription factor Fkh2 regulates the cell division cycle of Schizosaccharomyces pombe. Eukaryotic Cell 2004, 3(4), 944-954.
- Stiefel J, Wang L, Kelly DA, Janoo RTK, Seitz J, Whitehall SK, Hoffman CS. Suppressors of an adenylate cyclase deletion in the fission yeast Schizosaccharomyces pombe. Eukaryotic Cell 2004, 3(3), 610-619.
- Greenall A, Hadcroft AP, Malakasi P, Jones N, Morgan BA, Hoffman CS, Whitehall SK. Role of fission yeast Tup1-like repressors and Prr1 transcription factor in response to salt stress. Molecular Biology of the Cell 2002, 13(9), 2977-2989.
- Borrelly GPM, Harrison MD, Robinson AK, Cox SG, Robinson NJ, Whitehall SK. Surplus zinc is handled by Zym1 metallothionein and Zhf endoplasmic reticulum transporter in Schizosaccharomyces pombe. Journal of Biological Chemistry 2002, 277(33), 30394-30400.
- Robinson NJ, Whitehall SK, Cavet JS. Microbial metallothioneins. Advances in Microbial Physiology 2001, 44, 183-213.
- Janoo RTK, Neely LA, Braun BR, Whitehall SK, Hoffman CS. Transcriptional regulators of the Schizosaccharomyces pombe fbp1 gene include two redundant Tup1p-like corepressors and the CCAAT binding factor activation complex. Genetics 2001, 157(3), 1205-1215.
- Whitehall S, Stacey P, Dawson K, Jones N. Cell cycle-regulated transcription in fission yeast: Cdc10-Res protein interactions during the cell cycle and domains required for regulated transcription. Molecular Biology of the Cell 1999, 10(11), 3705-3715.
- Zhu Y, Takeda T, Whitehall S, Peat N and Jones N. Functional characterization of the fission yeast start-specific transcription factor Res2. Embo Journal 1997, 16, 1023-1034.
- Whitehall SK Kassavetis GA and Geiduschek EP. The symmetry of the yeast U6 RNA gene's TATA box and the orientation of the TATA-binding protein in yeast TFIIIB. Genes and Development 1995, 9, 2974-2985.