Maeshima Group / Genome Dynamics Laboratory

Liquid-like chromatin in the cell: What can we learn from imaging and computational modeling?

Yuji Itoh, Esmae J. Woods, Katsuhiko Minami, Kazuhiro Maeshima, and Rosana Collepardo-Guevara

Current Opinion in Structural Biology 71, 123-135 (2021) DOI:10.1016/j.sbi.2021.06.004

The loopy world of cohesin.

Kazuhiro Maeshima and Shiori Iida

eLife 10, e71585 (2021) DOI:10.7554/eLife.71585

Chromatin in eukaryotic cells is a negatively charged long polymer consisting of DNA, histones, and various associated proteins. With its highly charged and heterogeneous nature, chromatin structure varies greatly depending on various factors (e.g., chemical modifications and protein enrichment) and the surrounding environment (e.g., cations): From a 10-nm fiber, a folded 30-nm fiber, to chromatin condensates/droplets. Recent advanced imaging such as single-nucleosome imaging (Figure 1A) has observed that chromatin exhibits a dynamic liquid-like behavior and undergoes structural variations within the cell (Figure 1B). Current computational modeling has made it possible to reconstruct the liquid-like chromatin in the cell by dealing with a number of nucleosomes on multi-scale levels, and has become a powerful technique to inspect the molecular mechanisms giving rise to the observed behavior, which imaging methods cannot do on their own (Figure 1C). Based on new findings from both imaging and modeling studies, we discuss the dynamic aspect of chromatin in living cells and its functional relevance.

This work was supported by JSPS grant (19K23735, 20J00572, 20H05936, 21H02453), the Takeda Science Foundation, the Uehara Memorial Foundation, NIG Postdoctoral Fellowship, JSPS Postdoctoral Fellowship (PD).

Also, on July 26th, a professor at Genome Dynamics Laboratory Kazuhiro Maeshima and SOKENDAI Ph.D. student Shiori Iida published an Insight paper in eLife. Chromatin higher-order structures, such as chromatin loop domains, are critical for chromatin to perform various functions in the cell. The formation of these chromatin loops is thought to be mediated by a ring-shaped molecular complex, cohesin (Figure 2, left). Currently, the mechanism of chromatin loop formation is a hot topic in cell biology, and a model called loop extrusion, in which cohesin pushes DNA out of the ring, has been attracting much attention. In fact, cohesin has been shown to extrude naked DNA in vitro. Recently, Dr. Frank Uhlmann and his colleagues have shown how cohesin excludes DNA loops in vitro (Figure 2, bottom)(Higashi et al., “A Brownian ratchet model for DNA loop extrusion by the cohesin complex”. eLife, 2021 DOI:10.7554/eLife.67530). Based on the Higashi et al. paper, Maeshima and Iida discussed the intracellular behavior of cohesin and whether the loop extrusion reported really occurs in the cell.

Estrogens influence female itch sensitivity via the spinal gastrin-releasing peptide receptor neurons

K. Takanami*, D. Uta, K. Matsuda, M. Kawata, E. Carstens, T. Sakamoto, and H. Sakamoto
*Corresponding author

PNAS 118, e2103536118 (2021) DOI:10.1073/pnas.2103536118

Press release (In Japanese only)

“Itch” sensitivity in women changes during periods when female sex hormones fluctuate, such as during pregnancy and menopause. Especially, many women exhibit itch symptoms during pregnancy, but the underlying mechanism of the change in itch sensitivity is unknown. Here Dr. Takanami et al. demonstrate that estradiol, but not progesterone, enhances histamine-evoked itch-related scratching behavior in female rats. This is associated with the enhancement of activity of “gastrin-releasing peptide receptor (GRPR)” neurons in the spinal cord (Fig. 1). The findings suggest that female hormone, estrogens selectively enhance histamine-evoked itching by regulating spinal GRP system in females (Fig. 2). This may account for why itch sensation varies across the female lifecycle and provides a novel basis for treating itchy diseases in females.

▶ This article was seleceted “In This Issue” of PNAS.

PZLAST: an ultra-fast amino acid sequence similarity search server against public metagenomes

H. Mori, H. Ishikawa, K. Higashi, Y. Kato, T. Ebisuzaki, K. Kurokawa

Bioinformatics 2021 July 7 DOI:10.1093/bioinformatics/btab492

Press release (In Japanese only)

Similarity searches of amino acid sequences against the public metagenomic data can provide users insights about the function of sequences based on the environmental distribution of similar sequences. However, a considerable reduction in the amount of data or the accuracy of the result was necessary to conduct sequence similarity searches against public metagenomic data, because of the vast data size more than Terabytes. Here, we present an ultra-fast service for the highly accurate amino acid sequence similarity search, called PZLAST, which can search the user’s amino acid sequences to several Terabytes of public metagenomic sequences in approximately 10-20 minutes. PZLAST accomplishes its search speed by using PEZY-SC2, which is a MIMD many-core processor. Results of PZLAST are summarized by the ontology-based environmental distribution of similar sequences. PZLAST can be used to predict the function of sequences and mine for homologs of functionally important gene sequences.

Source: H. Mori, et al., Bioinformatics DOI: 10.1093/bioinformatics/btab492

▶ PZLAST is available here.