SEMINAR @ SISSA, SBP, dr. T. Sexton - May 30, at 14.00 hrs.

[Barbara Corzani]

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STATISTICAL AND BIOLOGICAL PHYSICS SEMINAR
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Dr. Thomas Sexton

(IGH CNRS - Montpellier)

 

Title:

"Global mapping of genomic spatial interactions in the fruit fly"

 

Mon 30 May, 2011 @ 02.00 p.m.

 

SISSA - first floor - room 132
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The nucleus is a highly heterogeneous organelle, with a non-random spatial
arrangement of the genome and the factors that process it, such as the DNA
replication and transcription machinery. At one level, it has been shown
that regulatory DNA elements can exert effects on target genes over
distances of hundreds of kilobases, and that these effects are often
correlated with physical contact of the target gene. At a higher level,
genes from the same and different chromosomes have been found to spatially
cluster at nuclear foci that are enriched in their regulatory factors,
indicating that groups of genes may be co-ordinately regulated via their 3-D
organisation.

A molecular approach, termed 3C (chromosome conformation capture), allows
the detection of DNA fragments that are spatially proximal in vivo, and this
technique has been combined with high-throughput sequencing in order to gain
a more comprehensive catalogue of pairwise genomic interactions within the
nucleus, and hence a spatial map of the genome. We have developed a Hi-C
approach and have used it to map genomic interactions within the developing
embryo of the fruit fly, Drosophila. From preliminary experiments, we have
recapitulated known bulk behaviours of Drosophila chromosomes and have
identified many known and novel interactions, already at a resolution
surpassing previous reports for multicellular organisms. A subset of these
interactions is perturbed by mutation of a key protein required for stable
silencing of many developmental genes, linking genome organisation and
functional regulation. With deeper sequencing and extension to various
different mutants, we hope to determine which genomic interactions are
functionally regulated, and dissect their mechanisms at very high
resolution.