Systems Biology of nuclear organization of the genome and non-coding RNAs

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Until recently it was believed that the only function of DNA was to encode RNA transcripts that were then translated into proteins. However it is now known that 60-90% of the genome is transcribed and less than 10% of the DNA sequence copied into RNA actually functions to make proteins. Many of the non-protein coding transcripts are highly unstable or rare and their function is being investigated. Other non-coding transcripts stably accumulate and appear to function in regulating gene expression over wide areas of the genome. Folding of the genome in three dimensions is also important in determining which parts of the genome are active in different cell types. Our work has shown genome conformation is non random and tissue specific and plays an important role in coordinating transcription of co-regulated and co-functional genes. ncRNAs affect genome conformation and nuclear compartmentalization and therefore influence gene expression. We will investigate nuclear organization and compartmentalization. These experiments will provide important insights into the regulation of the genome with a significant impact on human health.

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