Biology subjects

Nakazawa, Y.

Publications and source records attributed to Nakazawa, Y..

4 recordsLinked to original sources

bioRxiv2021

Cluster Analysis of SARS-CoV-2 Gene using Deep Learning Autoencoder: Gene Profiling for Mutations and Transitions

We report on a method for analyzing the variant of coronavirus genes using autoencoder. Since coronaviruses have mutated rapidly and generated a large number of genotypes, an appropriate method for understanding the entire population is required. The method using autoencoder meets this requirement and is suitable for understanding how and when the variants emarge and disappear. For the over 30,000 SARS-CoV-2 ORF1ab gene sequences sampled globally from December 2019 to February 2021, we were able to represent a summary of their characteristics in a 3D plot and show the expansion, decline, and transformation of the virus types over time and by region. Based on ORF1ab genes, the SARS-CoV-2 viruses were classified into five major types (A, B, C, D, and E in the order of appearance): the virus type that originated in China at the end of 2019 (type A) practically disappeared in June 2020; two virus types (types B and C) have emerged in the United States and Europe since February 2020, and type B has become a global phenomenon. Type C is only prevalent in the U.S. and is suspected to be associated with high mortality, but this type also disappeared at the end of June. Type D is only found in Australia. Currently, the epidemic is dominated by types B and E.

microbiology↗

bioRxiv2021

ELOF1 is a transcription-coupled DNA repair factor that directs RNA polymerase II ubiquitylation

Cells employ transcription-coupled repair (TCR) to eliminate transcription-blocking DNA lesions. The binding of the TCR-specific repair factor CSB triggers DNA damage-induced ubiquitylation of RNA polymerase II (RNAPII) at a single lysine (K1268) by the CRL4CSA ubiquitin ligase. However, how the CRL4CSA ligase is specifically directed toward the K1268 site is unknown. Here, we identify ELOF1 as the missing link that facilitates RNAPII ubiquitylation, a key signal for the assembly of downstream repair factors. This function requires its constitutive interaction with RNAPII close to the K1268 site, revealing ELOF1 as a specificity factor that positions CRL4CSA for optimal RNAPII ubiquitylation. Furthermore, drug-genetic interaction screening reveals an unanticipated compensatory TCR pathway in which ELOF1 together with known factors DOT1L and HIRA protect CSB-deficient cells from collisions between transcription and replication machineries. Our study provides a genetic framework of the transcription stress response and reveals key insights into the molecular mechanism of TCR.

molecular biology↗

bioRxiv2020

Tumor-derived extracellular vesicles regulate tumor-infiltrating regulatory T cells via the immunoreceptor CD300a

Although tumor-infiltrating regulatory T (Treg) cells play a pivotal role in tumor immunity, how Treg cell activation are regulated in tumor microenvironments remains unclear. Here, we found that mice deficient in the inhibitory immunoreceptor CD300a on their dendritic cells (DCs) have increased numbers of Treg cells in tumors and greater tumor growth compared with wild-type mice after transplantation of B16 melanoma. Pharmacological impairment of extracellular vesicle (EV) release decreased Treg cell numbers in CD300a-deficient mice. Coculture of DCs with tumor-derived EV (TEV) induced the internalization of CD300a and the incorporation of EVs into endosomes, in which CD300a inhibited TEV-mediated TLR3-TRIF signaling for activation of the IFN-{beta}-Treg cells axis. We also show that higher expression of CD300A was associated with decreased tumor-infiltrating Treg cells and longer survival time in patients with melanoma. Our findings reveal the role of TEV and CD300a on DCs in Treg cell activation in the tumor microenvironment.

cancer biology↗

bioRxiv2020

Genome sequence of Hydrangea macrophylla and its application in analysis of the double flower phenotype

Owing to its high ornamental value, the double flower phenotype of hydrangea (Hydrangea macrophylla) is one of its most important traits. In this study, genome sequence information was obtained to explore effective DNA markers and the causative genes for double flower production in hydrangea. Single molecule real-time sequencing data followed by a HiC analysis was employed. The resultant haplotype-phased sequences consisted of 3,779 sequences (2.256 Gb in length and N50 of 1.5 Mb), and 18 pseudomolecules comprising 1.08 Gb scaffold sequences along with a high-density SNP genetic linkage map. Using the genome sequence data obtained from two breeding populations, the SNPs linked to double flower loci (Djo and Dsu), were discovered for each breeding population. DNA markers J01 linked to Djo and S01 linked to Dsu were developed, and these could be used successfully to distinguish the recessive double flower allele for each locus respectively. The LEAFY gene was suggested as the causative gene for Dsu, since frameshift was specifically observed in double flower accession with dsu. The genome information obtained in this study will facilitate a wide range of genomic studies on hydrangea in the future.

genomics↗