Research Groups >  (CSC Associated Investigators) Genome Function

“The structural organisation of chromatin affects the expression of genes – we study this relationship in embryonic stem (ES) cells and differentiated systems”

Our main aim is to understand the molecular and structural processes that regulate gene expression in the context of the interphase nucleus. We are investigating the relationship between genome architecture and gene expression in embryonic stem (ES) cells and differentiated systems.

Using chromatin immunoprecipitation (ChIP), we have shown that poised RNA polymerase II complexes are bound in ES cells at inactive, PRC-repressed genes that are important for early ES cell differentiation. We are currently studying their activity and regulation – and characterizing RNA polymerase II modification using genomewide ChIP mapping – through the Illumina platform. We have developed high-resolution imaging methods for the visualisation of spatial relationships within the nucleus (cryo-FISH), and aim to understand the contribution of nuclear positioning on gene expression. We are using biochemical strategies to identify regulators of RNA polymerase II function in a bid to devise genetic assays that directly test their roles in genome architecture and gene regulation.
 


Figure 3. Association of active genes (red) with transcription factories (green) in T cells.

 Genome Function
Group head

Ana Pombo (Professor)

Telephone 38232
Email
Group members

Robert Beagrie (Mr)

PhD Student
Telephone 38269
Email

Mita Chotalia (Dr)

Telephone 38269
Email

Kelly Morris (Ms)

Telephone 38269
Email

Sheila Quingchun Xie (Dr)

Telephone 34154
Email
Visiting worker

Ines Castro

Telephone 38269
Email
Contact details
Telephone: +44 (0) 20 8383 8232
Facsimile: +44 (0) 20 8383 8306
Selected publications
Barbieri, M., Chotalia, M., Fraser, J., Lavitas, L.-M. M., Dostie, J., Pombo, A., Nicodemi, M., (2012). Complexity of chromatin folding is captured by the strings and binders switch model. Proceedings of the National Academy of Sciences of the United States of America 109 (40), 16173-16178. Abstract

Brookes E, de Santiago I, Hebenstreit D, Morris KJ, Carroll T, Xie SQ, Stock JK, Heidemann M, Eick D, Nozaki N, Kimura H, Ragoussis J, Teichmann SA, Pombo A (2012) Polycomb Associates Genome-wide with a Specific RNA Polymerase II Variant, and Regulates Metabolic Genes in ESCs. Cell Stem Cell, 10, 157-170. Abstract

Moeller A, Xie SQ, Hosp F, Lang, B, Phatnani HP, James S, Ramirez F, Collin GB, Naggert JK, Babu MM, Greenleaf AL, Selbach M, Pombo A (2011) Proteomic analysis of mitotic RNA polymerase IIreveals novel interactors and association withproteins dysfunctional in disease. Molecular & Cell Proteomics, 11, M111.011767. Abstract

Ferrai, C., Xie, S. Q., Luraghi, P., Munari, D., Ramirez, F., Branco, M. R., Pombo, A., Crippa, M. P. (2010). Poised Transcription Factories Prime Silent uPA Gene Prior to Activation. PLoS Biol. 8(1): e1000270 Abstract

Stock, J. K., Giardrossi, S., Casanova, M., Brookes, E., Vidal, M., Koseki, H., Brockdorff, N., Fisher, A. G. & Pombo, A. (2007). Ring1-mediated ubiquitination of H2A restrains poised RNA polymerase II at bivalent genes in mouse ES cells. Nature Cell Biology 9, 1428-1435. Abstract

Branco M. R. & Pombo A. (2006). Intermingling of chromosome territories in interphase suggests role in translocations and transcription-dependent associations. PLoS Biology 4, e138. Abstract | Full text

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