An international collaborative team, which was led by B.D. Rowland at the Netherlands Cancer Institute and E. Lieberman Aiden (NIG International Strategic Advisor) at Baylor College of Medicine, investigated genome folding across the eukaryotic tree of life (24 species, Fig. B). The team found four types of 3D genome architecture at chromosome-scale (Fig. A). Each type appeared and disappeared repeatedly during eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with the absence of condensin II subunits (Fig. B). Condensin is a protein complex required for mitotic chromosome assembly. In vertebrates, it is known that there are two types of condensins, condensin I and II, and that condensin II shortens mitotic chromosomes.

Moreover, the team demonstrated that condensin II depletion converted the architecture of the human genome to a state resembling that seen in organisms such as fungi or mosquitoes (Rabl-like, Fig. C). In this state, centromeres clustered together at nucleoli, and heterochromatin domains merged. The team proposed a physical model in which lengthwise compaction of chromosomes by condensin II during mitosis determines chromosome-scale genome architecture, with effects that are retained during the subsequent interphase. This mechanism is likely conserved since the last common ancestor of all eukaryotes.

The part to which NIG contributed was supported by MEXT KAKENHI grants (20H05936).

Figure: (A) Chromosome positioning in the nucleus classified by Hi-C maps: “chromosome territory” and “rabl-like”. (B) Hi-C maps of 24 species covering animals (yellow), fungi (blue) and plants (green). Presence of the condensin II subunits in each species is indicated by solid black circles. In case of condensin II-deficiency, shown as “Con IIΔ”. (C) Model. Having shorter chromosomes during cell division leads to separate centromeres and territorial genome architecture in the subsequent interphase. Reducing chromosome lengthwise compaction by condensin II disruption, leads to enhanced centromere clustering, loss of chromosome territories, and a Rabl-like genome architecture.

Press release

Press release (In Japanese only)

Neuronal birthdate is one of the major determinants of neuronal phenotypes. However, most birthdating methods are retrospective in nature, allowing very little experimental access to the classified neuronal subsets. Hirata and her collaborators have developed four neurogenic tagging mouse lines that can assign CreER-loxP recombination to neuron subsets that share the same differentiation timing in living animals. Because this genetic tag is irreversible, the classified neuronal subset can be subsequently subjected to various experimental manipulations.

To encourage the use of this resource, Hirata et al. have launched “NeuroGT database”, a brain atlas of neurogenic tagging mouse lines, which includes holistic image data of the loxP-recombined neurons and their processes across the entire brain that were tagged at each single day during the neurodevelopmental period. Users can search for the datasets from a web browser using the terns in the meta-information, interactively view thumbnail images of the sections, and download the high-resolution section images.

The NeuroGT is now open to public, offering people the opportunity to find specific neurogenic tagging driver lines and the stages of tagging appropriate for their own research purposes. The driver mouse lines can be obtained from Riken Bioresource Center.

The NeuroGT database was constructed by joint efforts of different research groups; mouse engineering (RIKEN Center for Biosystems Dynamics Research), neuroscience (National Institute of Genetics), bioimaging (National Institute for Basic Biology), and image informatics (Ritsumeikan University, RIKEN Center for Biosystems Dynamics Research)

This research was supported by ROIS Challenging Exploratory Research Projects for the Future Grant and Grant-in-Aid for Publication of Scientific Research Results (Database, 19HP7002). High resolution digitization of section images was supported by Advanced Bioimaging Support (JP16H06280) and Grants-in-Aid for Scientific Research (20H03345, JP18H05412).

• You can use the database here.

Figure: Graphical abstract of “NeuroGT Database”

Video: Thumbnail images of coronal sections can be sequentially viewed along the antero-posterior brain axis by dragging the slider. The images stained for the two different reporters, membrane-localized GFP and nucleus-localized-βGAL are stacked separately. The sync button automatically matches the section level of the two reporter images.

Left, Heita Kawakatsu (Governor, Shizuoka Prefecture): Right, Fumio Hanaoka (Director-General, National Institute of Genetics)