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Nick Gilbert — Effect of DNA supercoiling on chromatin structures

Speaker :

Nick Gilbert, Edinburgh Cancer Research Centre

When :

Wednesday 2 June at 11am

Where :

Amphi C

Title :

Effect of DNA supercoiling on chromatin structures

Abstract :

In mammalian cells transcription influences large scale chromatin compaction by an unknown mechanism. To identify the factors responsible we analysed human female active and inactive X chromosomes and showed that transcriptionally active large scale chromatin structures are torsionally constrained and their compaction is topoisomerase dependent. Transcriptional activation is accompanied by decompaction of large scale chromatin structures correlating with the production of short RNA transcripts upstream of genes, by the initiating form of RNA polymerase. Using a new approach we directly monitored the production of torsional stress in vivo at gene promoters by interchelating biotinylated psoralen into the DNA. Negative supercoils are introduced upstream of genes prior to transcriptional elongation introducing torsional stress and priming the locus for subsequent transcription consistent with the transcriptionally inactive X being in a torsionally relaxed conformation. We propose that torsional stress, generated by transcription, is transmitted through the chromatin fibre decompacting large scale chromatin structures.

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