Finally, we propose a model in which chromatin is self-organising based on histone acetylation and nucleosome depletion. We hypothesise that active cis-regulatory elements may contact one another at or above a layer of acetylated nucleosomes.

We then collaborated with Lothar Schermelleh to undertake super-resolution microscopy of chromatin acetylation. In keeping with his previous work we find that histone acetylation maps to regions of chromatin that are adjacent to the interchromatin compartment.

And histone acetylation drive the formation of the nanoscale domains we see in the MCC data.

This leads us to conclude that the biophysical properties of chromatin, particularly nucleosome depletion and histone acetylation, drive fine scale structure.

We show that nucleosome depletion....

In collaboration with Rosana Collepardo-Guevara who has develops a chemically specific molecular dynamic simulation of the physicochemical properties of chromatin, we constructed an MD simulation of the Myc promoter that closely matches the MCC data.

However, at other sites only the intricate structure of the nucleosome depleted region changes.

From this we conclude that nucleosome depletion itself is a major driver of long-range contacts.

At some sites SOX2 depletion causes complete collapse of the nucleosome depleted region at the enhancer and loss of all contacts.

We are able to map specific structures within the nucleosome depleted regions at regulatory elements that are driven by transcription factors.

Between nucleosome depleted regions we see nanoscale domains, that appear similar to TADs but are approximately 100- to 1000-fold smaller

Our latest paper has just been published in Cell!

doi.org/10.1016/j.ce...

We developed a new method called MCC ultra, which allows 3D chromatin structure to be visualised with a 1 base pair pixel size.