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Statistical Mechanics in Systems Biology: Villa Orlandi, Anacapri ~ May 29 - June 1, 2012 |
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Ana Pombo MRC Clinical Sciences Centre, Imperial College London, London (UK) From epigenetics to polymer models to single cell imaging: a tale of the HoxB locus Long-range chromatin interactions have been identified as major regulators of gene expression and chromosome organization. To investigate the mechanisms of chromatin folding and interaction, we used as model system a 1Mb genomic region including active genes and a cluster of HoxB genes. In embryonic stem (ES) cells, the HoxB genes are repressed by Polycomb-repressor complexes. Active genes are known to interact at active transcription factories, whereas Polycomb-repressed genes associate with poised transcription factories (Ferrai et al. 2010, Brookes et al. 2012). Using epigenetic mapping, we classified all the genes across the 1 Mb genomic region according to their activity status in ES cells (active, repressed or inactive). We used a simple polymer model (Nicodemi et al. 2008, Nicodemi and Prisco, 2009) to determine the different scenarios of 3D folding of the HoxB genomic region in the presence of each kind of factory separately or together. Using high-resolution imaging by cryo-FISH, we show that both active and poised transcription factories contribute to the 3D folding of the locus. We also identify novel examples of gene co-association at the same transcription factory, and begin to explore the effects of genomic context on the 3D interaction behavior of single genes.
Ferrai C et al. (2010) Poised transcription factories prime silent uPA genes prior to activation. PLoS Biol. 8, e1000270. |
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