Department of Physiology, Development and Neuroscience

Reader in Developmental Biology
Tel: +44 (0)1223 768080, Fax: +44 (0)1223 333840, E-mail: rw108@cam.ac.uk

Genomic approaches to transcriptional regulation and chromosome organisation in Drosophila

Our main focus is the investigation of the regulatory architecture of the genome through developing and exploiting genomic technologies in Drosophila. In particular we are using Chromatin immunopurification coupled with genomic microarray for large-scale analysis of the target sites of transcription factors and other DNA-binding and chromatin-associated proteins in the Drosophila genome. In collaboration with Steve Russell’s lab in the Dept of Genetics/Cambridge Systems Biology Centre, we have carried out analyses of the genomic targets of insulators and silencers and the Hox transcription factors. This has provided insight into the roles of insulators and silencers and, for example, we have shown that the insulator protein CTCF bounds defined regulatory domains in the Bithorax complex. Our studies on Hox protein binding have emphasised the role of chromatin accessibility in Hox target selection.

(Fig. Drosophila spermatocyte nucleus; histones in green and the red reveals the Y-loops. )

Our main interests are:
• The development of ChIP-array technology in the fly including the scaling down for analysis of defined in vivo cell states.
• Analysis of the regulatory architecture of the genome through the genomic mapping of the binding sites of chromatin-associated proteins, especially proteins associated with insulator function and the analysis of the connection between chromosomal architecture and transcriptional regulation.
• The identification of targets of the Hox genes in Drosophila. The Hox genes form a genetic code that specifies position along the antero-posterior body axis. They are the key regulators that specify the differences between segmental morphologies. We are investigating the basis of the specificity of the different Hox genes and the role of Hox-cofactors such as Extradenticle.
• We are also interested in the links between chromatin organisation in the nucleus and the regulation of gene expression and we are investigating the nuclear organisation of gene expression in the large and highly organised nucleus of the primary spermatocyte.

Team members:
Paolo Magbanua (Post-doc)
Sherif El Sharnouby (Post-doc)
Katerina Chatzipli (Post-graduate student)

Selected publications:
Holohan, E. E., Kwong, C., Adryan, B., Bartkuhn, M., Herold, M., Renkawitz, R., Russell, S. and White, R. (2007) CTCF Genomic Binding Sites in Drosophila and the Organisation of the Bithorax Complex. PLoS Genet 3:e112.

Adryan, B.,Woerfel, G., Birch-Machin, I., Gao, S., Quick, M.,, Meadows, L., Russell, S. and White, R. (2007) Genomic mapping of Suppressor of Hairy-wing binding sites in Drosophila. Genome Biol. 8:R167.

Mohan, M., Bartkuhn, M., Herold, M., Philippen, A., Heinl, N., Bardenhagen, I., Leers, J., White, R., Renkawitz-Pohl, R., Saumweber, H. and R. Renkawitz (2007) The Drosophila insulator proteins CTCF and CP190 link enhancer blocking to body patterning. EMBO J. 26: 4203-14.

Kwong, C., Adryan, B., Bell, I., Meadows, L., Russell, S., Manak, J. R., White, R. (2008) Stability and dynamics of Polycomb target sites in Drosophila development. PLoS Genet 4:e1000178

ModENCODE Consortium [including White, R] (2011) A cis-regulatory map of the Drosophila genome. Nature 471: 527-31.

Choo SW, White R and S Russell (2011) Genome-wide analysis of the binding of the Hox protein Ultrabithorax and the Hox cofactor Homothorax in Drosophila. PLoS ONE 6: e14778.

Redhouse, J. L., Mozziconacci, J. and White, R. A. (2011) Co-transcriptional architecture in a Y loop in Drosophila melanogaster. Chromosoma 12: 0399-407