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A quantitative view of gene expression levels and epigenetic modifications

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Gene expression levels are believed to be continuously distributed from very low to very high levels, with most genes at an intermediate level. We have studied the transcriptome-wide distribution of expression levels in T helper cells based on microarray and RNA -seq technology. We integrated this data with single molecule mRNA-fish experiments for well-characterized genes, allowing the quantification of mRNA transcripts at single-molecule resolution. The results of these analyses and experiments show that virtually all genes are expressed at > ~ 1 molecule per cell and that two major expression levels can be identified which vary by roughly one to two orders of magnitude, giving rise to strongly bimodal expression distributions. Analysis of histone modifications by ChIP-seq indicates that activating modifications such as H3K9 /14ac and H3K4me3 are involved in this ‘digital’ expression switch. Our findings have broad implications for the analysis of microarray, RNA -seq and ChIP-seq data and for the understanding of the regulation of gene expression.

Hosted by Florian Markowetz.

This talk is part of the Seminars on Quantitative Biology @ CRUK Cambridge Institute series.

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