Our group has an avid interest in distal regulatory elements and three-dimensional aspects of gene control, which largely developed after discovering a critical role for enhancers in cellular reprogramming. Central to this interest is to understand the importance of enhancers and insulators and how they contribute to the transformation process. We use cutting-edge genome-wide tools (eg. DNA methylation and nucleosome positioning (NOMe-Seq), chromatin interaction assays (ChIA-PET, Hi-C)) and bioinformatic analyses to address key questions concerning epigenetic reprogramming. This work will impact how therapeutic targets are defined and a focus on epigenetics provides an unequivocal opportunity to identify novel targets and develop cancer prevention measures.
Current areas of interest are:
- Long-range interactions and temporal regulation of the genome
- Global epigenetic signatures of reprogrammed distal regulatory elements
- Understanding the important role of the three-dimensional genome in normal and cancer biology
Our work has directly answered many unresolved questions, some of which had remained unanswered for over 30 years. These findings impact the multi-disciplinary fields of epigenetics, developmental gene regulation, embryonic stem cell biology and cellular reprogramming.
Brettingham-Moore KH, Taberlay PC, Holloway AF. (2015) Interplay between transcription factors and the epigenome: Insight from the role of RUNX1 in leukemia. Frontiers in Immunology. In press (accepted September 2015).
Qadi AA, Taberlay PC, Phillips JL, Young A, West AC, Brettingham-Moore KH, Dickinson JL, Holloway AF. (2015) The Leukemia Inhibitory Factor Receptor Gene is a Direct Target of RUNX1. Journal of Cellular Biochemistry. doi: 10.1002/jcb.25246 [Epub ahead of print].
Brettingham-Moore KH and Taberlay PC*. (2015) Cancer Epigenetics in Drug Discovery in Cancer Epigenetics. In press (accepted May 2015).
Aaron L. Statham, Phillippa C. Taberlay, Theresa K. Kelly, Peter A. Jones and Susan J. Clark. Genome-wide nucleosome occupancy and DNA methylation profiling of four human cell lines. Genome Data, 2015; 3:94-96
Phillippa C. Taberlay*, Aaron L. Statham*, Theresa K. Kelly, Susan J. Clark* and Peter A. Jones*. Reconfiguration of nucleosome depleted regions at distal regulatory elements accompanies DNA methylation of enhancers and insulators in cancer. Genome Research, 2014; 24(9):1421-1432.
Katherine A. Skulte, Lisa Phan, Susan J. Clark and Phillippa C. Taberlay. Chromatin remodeller mutations in human cancers: epigenetic implications. Epigenomics, 2014; 6(4):397-414
Daniel D. De Carvalho*, Shikhar Sharma*, Jueng Soo You, Sheng-Fang Su, Phillippa C. Taberlay, Theresa K. Kelly, Xiaojing Yang, Gangning Liang, and Peter A. Jones. DNA methylation screening identifies driver epigenetic events of cancer cell survival. Cancer Cell, 2012; 21(5):655 – 667.
Phillippa C. Taberlay, Theresa K. Kelly, Chun-Chi Lui, Jueng Soo You, Daniel D. de Carvalho, Tina B. Miranda, Xianghong J. Zhou, Gangning Liang, and Peter A. Jones. Polycomb repressed genes have permissive enhancers that initiate reprogramming. Cell, 2011; 47(6): 1283 – 1294.
Phillippa C. Taberlay and Peter A. Jones. DNA Methylation and Cancer. Prog Drug Res. 2011; 67:1-23.
Jueng Soo You, Theresa K. Kelly, Daniel D. de Carvalho, Phillippa C. Taberlay, Gangning Liang, and Peter A. Jones. OCT4 establishes and maintains nucleosome depleted regions which provide additional layers of epigenetic regulation of its target genes. PNAS 108(35):14497-14502.
Phillippa C. Oakford, Sally R. James, Abeer Qadi, Alison C. West, Shannon N. Ray, Andrew G. Bert, Peter N Cockerill and Adele F. Holloway. Transcriptional and epigenetic regulation of the GM-CSF promoter by RUNX1. Leukemia Research 2010; 34 (9):1203-1213.
Kate H. Brettingham-Moore, Owen. R. Sprod, Xin Xin Chen, Phillippa C. Oakford, M. Frances Shannon and Adele F. Holloway. Determinants of a Transcriptionally Competent Environment at the GM-CSF promoter. Nucleic Acids Research 2008; 36 (8): 2639-2653.
Adele F. Holloway and Phillippa C. Oakford. Targeting Epigenetic Modifiers in Cancer. Current Medicinal Chemistry 2007; 14 (24): 2540-2547.
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