Tobias Aurelius Knoch, Malte Wachsmuth, Nick Kepper, Michael Lesnussa, Anis Abuseiris, A. M. Ali Imam, Petros Kolovos, Jessica Zuin, Christel E. M. Kockx, Rutger W. W. Brouwer, Harmen J. G. van de Werken, Wilfred F. J. van IJken, Kerstin S. Wendt, Frank G. Grosveld
Review posted on 17th August 2016
I have read the paper “The Detailed 3D Multi-Loop Aggregate/Rosette Chromatin Architecture and Functional Dynamic Organization of the Human and Mouse Genomes.' by Tobias A. Knoch and colleagues with great satisfaction.
It is a sound done and written truly systems genomic paper combining selective high-throughput high-resolution chromosomal interaction capture (T2C), polymer simulations, and scaling analysis of the 3D-architecture and the DNA sequence.
It comes out with phenomenal results solving the debates on the 3D chromatin folding and architecture as they correctly write in their abstract: 'The genome is compacted into a chromatin quasi-fibre with ~5±1 nucleosomes/11nm, folded into stable ~30-100 kbp loops forming stable loop aggregates/rosettes connected by similar sized linkers.’
I appreciate this paper as myself saw and described the rosette-like DNA folding electronmicroscopically many years ago (Je. Erenpreisa, Organisation of the chromatin in interphase cell nucleus. 1990. Zinatne Publ. Riga (Russ); reviewed by Erenpreisa Je and Zhukotsky A. The genome field. Proc. Latv,. Acad.Sci, Ser.B 1992,3: 64-68) and now our mostly descriptive studies are so convincingly confirmed. As to the also much debated supranucleosomal structure with the basic unit of 5±1 nucleosomes, which tend to cluster, this finding correspond the cited model of Subirana et al. The layered organization of nucleosomes in 30 nm chromatin fibers FEBS Lett 1985, 91:377-390. It was based on di-nucleosomic zigzag layers, each composed of five nucleosomes (2X2 and 1 for a link between layers) and I also found zigzag structure to be most consistent. The nucleosome clusters or their oligomeric ‘superbeads’ first reported by Kiryanov GI, Manamshjan TA, Polyakov VYu, Fais D, Chentsov JuS Levels of granular organization of chromatin fibres. FEBS Letters 1976, 67:323-327) are likely easily formed on this base (5±1 nucleosomes). These clusters were seen in our lab by electron microscopy on thin section and chromatin spreads. So, the revealed periodicity also puts an end to the long-lasting debate on the structure of this level of DNA folding.
I have followed the work of Tobias Knoch for years and have listened to many great talks of him - but now really have to say that I am impressed by the clarity and consistency of the data and even the detailed arguments. I am also impressed that the T2C data, the scaling analysis and the analysis of the DNA sequence, as well as the simulations, are all in such an agreement.
The only question is, when we can also read the obviously co-submitted manuscript from Malte Wachsmuth ‘Dynamic properties of independent chromatin domains measured by correlation spectroscopy in living cells.’ which seems to come from the dynamic site and achieves the same results.
Thus, I conclude that Tobias Knoch and Malte Wachsmuth really have made a crucial step to pin down the long debated 3D chromatin architecture. Congratulations!