BIOQUANT

Nuclear Organization

Background

The cell nucleus and the genome are organized into spatially separated subcompartments although the nucleus does not contain any internal membranes. In this manner genome related activities like transcription, RNA processing or telomere maintenance are targeted to specific genomic loci. These subcompartment include DNA-containing 'chromatin bodies' like nucleoli, which are involved in ribosome biogenesis, transcription factories associated with active RNA polymerase II, as well as PcG bodies and pericentric heterochromatin foci (referred to as chromocenters due to their intense staining with DAPI in fluorescence microscopy images), which contain facultative and constitutive heterochromatin, respectively. Other subcompartments like PML nuclear bodies (PML-NBs) or paraspeckles are mostly devoid of DNA but can associate with certain genomic loci or contain RNA as a structural scaffold. Most protein components that define these structures are small enough to rapidly move across the nucleoplasm, i.e., the liquid phase that fills the nucleus Thus,it is a pertinent question how these nuclear subcompartments are stabilized although diffusion balances concentration gradients.

Work of the group

We study PML nuclear bodies, which are involved in telomere maintenance, dense heterochromatin foci, which contain repressed genes, and the nucleolus, which is the site of active transcription of ribosomal RNA. We investigate the properties of these assemblies by quantitative fluorescence microscopy and deep sequencing, predict their impact on epigenetic regulation using network modeling, and probe their assembly mechanism and stability by chromatin editing.

 

Figure 1. Nuclear compartmentalization. (A) The nucleus contains several subcompartments, such as PML nuclear bodies or heterochromatic chromocenters. (B) Chromatin subcompartments can be stabilized by multivalent bridging factors. (C) Compartmentalization is related to the biological activity of the respective chromatin region.

 

Selected references

Rademacher A, Erdel F, Trojanowski J, Schumacher S & Rippe K (2017). Real-time observation of light-controlled transcription in living cells. J Cell Sci 130, 4213-4224. doi: 10.1242/jcs.205534 | Abstract | Reprint (12.9 MB) | JCS First person | Article metrics

Molitor J, Mallm JP, Rippe K & Erdel F (2017). Retrieving chromatin patterns from deep sequencing data with correlation functions. Biophys J 112, 473-490. doi: 10.1016/j.bpj.2017.01.001 | Abstract | Reprint (10.3 MB) | Software | Article metrics.

Wachsmuth M, Knoch TA & Rippe K (2016). Dynamic properties of independent chromatin domains measured by correlation spectroscopy in living cells. Epigenetics Chromatin 9, 57. doi: 10.1186/s13072-016-0093-1 | Abstract | Reprint (5.1 MB) | Article metrics.

Cremer T, Cremer M, Hübner B, Strickfaden H, Smeets D, Popken J, Sterr M, Markaki Y, Rippe K & Cremer C (2015). The 4D nucleome: evidence for spatially co-aligned active and inactive nuclear compartments and their functional implications. FEBS Lett 589, 2931-2943. doi: 10.1016/j.febslet.2015.05.037 | Abstract | Reprint (2.2 MB) | Article metrics

Caudron-Herger M, Pankert T, Seiler J, Nemeth A, Voit R, Grummt I & Rippe K (2015). Alu element-containing RNAs maintain nucleolar structure and function. EMBO J 34, 2758-2771. doi: 10.15252/embj.201591458 | Abstract | Reprint (4.6 MB) | Comment | Cover | Article metrics

Osterwald S, Deeg KI, Chung I, Parisotto D, Wörz S, Rohr K, Erfle H & Rippe K (2015). PML induces compaction, partial TRF2 depletion and DNA damage signaling at telomeres and promotes alternative lengthening of telomeres. J Cell Sci 128, 1887-1900. doi: 10.1242/jcs.148296 | Abstract | Reprint (4.3 MB) | Article metrics

Müller-Ott K, Erdel F, Matveeva A, Hahn M, Mallm, JP, Rademacher A, Marth C, Zhang Q, Kaltofen S, Schotta G, Höfer T & Rippe K (2014). Specificity, propagation and memory of pericentric heterochromatin. Mol Syst Biol 10, 746. doi: 10.15252/msb.20145377 | Abstract | Reprint (7.4 MB) | Article metrics

Baum M, Wachsmuth M, Erdel F & Rippe K (2014). Retrieving the intracellular topology from multi-scale protein mobility mapping in living cells. Nat Commun 5, 4494. doi: 10.1038/ncomms5494 | Abstract | Reprint (6.4 MB) | Article metrics

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