Gene Expresion Regulation: Chromatin Remodelling

Source: Hirota et al. (2008). Stepwise chromatin remodelling by a cascade of transcription initiatoin of non-coding RNAs. Nature 456:130-134.

The RNA-seq strategy has revolutionized our way of doing biology, but it has also complicated the way we used to look at gene expression regulation. First, it has been shown that a huge number of RNAs are produced without ever being translated. Many of these species are envisioned to participate in some sort of expression regulation... In this paper, the authors make the case for one such mechanism: firing from upstream promoters results in chromatin modifications that leads to the activation of the main promoter.

While studying the regulation on fbp 1+ in yeast, the authors observed that upon starvation it takes around 60 min for the main RNA to show up; however, during this period 3 other longer RNAs show up suggesting active upstream promoters (a, b and c in figure below). Using chromatin-IP for RNApolII, they confirmed the occupation of these upstream promoters upon activation. They also assyed chromatin remodelling using MNase assay to show that the chromatin is in fact modified upon activation.
The key point here, however, was the fact that upon cloning a transcription termination site between the upstream promoters and the main promoter inhibits activation... which means transcription is required for the observed chromatin remodelling. The figure below, from the original paper, shows the details of this mechanism.