User:Bursting74

Transcriptional bursting

A fundamental property of genes from prokaryotes such as E.coli up to humans. Transcription of genes, the process which transforms the code written in DNA into the mobile RNA message can occur in "bursts" or "pulses". This phenomenon has recently come to light with the advent of new technologies to detect RNA production in single cells, allowing precise measurements of RNA number, or RNA appearance at the gene. Older, more standard techniques, such as Northern Blotting, Microarrays or RT-PCR, measure Bulk RNA levels from homogenous population RNA extracts. These techniques lose dynamic information from individual cells, and gives the impression transcription is a continuous smooth process. The reality is that transcription is irregular, with strong periods of activity, interspersed by long periods of inactivity. Averaged over millions of cells, this appears continuous. But at the individual cell level, there is considerable variability, and for most genes, very little activity at any one time.

Bursting is hypothesised to result from the stochastic nature of biochemical events superimposed upon a 2 or more step fluctuation. In its most simple form, the gene can exist in 2 states, one where activity is impossible and one where there is a certain probability of activation. Only in the second state can transcription occur. Whilst the nuclear and signalling landscapes of complex eukaryotic nuclei is likely to favour more than two simple states- for example, there are over twenty post-translation modifications of nucleosomes known, this simple two step model perhaps provides a reasonable intellectual framework for understanding the changing probabilities affecting transcription.

What do the open and closed states represent? An attractive idea is that the repressed state is a closed chromatin conformation whilst the open state is a permissive one. Another hypothesis is that the fluctuations reflect transition between bound pre-initiation complexes (permissive) and dissociated one (restrictive). Bursts may also result from bursty signalling, or cell cycle effects. It seems likely that some rudimentary eukaryotes have genes which do not show bursting. The genes are always in the permissive state, with a simple probability describing the numbers of RNAs generated.