Tuning of Sry expression by H3K9 methylation and demethylation

Histone H3 lysine 9 (H3K9) methylation is a hallmark of heterochromatin. H3K9 demethylation is crucial in mouse sex determination; The H3K9 demethylase Jmjd1a deficiency leads to increased H3K9 methylation at the Sry locus in embryonic gonads, thereby compromising Sry expression and causing male-to-female sex reversal. We hypothesized that the H3K9 methylation level at the Sry locus is finely tuned by the balance in activities between the H3K9 demethylase Jmjd1a and an unidentified H3K9 methyltransferase to ensure correct Sry expression. Here we identified the GLP/G9a H3K9 methyltransferase complex as the enzyme catalyzing H3K9 methylation at the Sry locus. Based on this finding, we tried to rescue the sex-reversal phenotype of Jmjd1a-deficient mice by modulating GLP/G9a complex activity. A heterozygous GLP mutation rescued the sex-reversal phenotype of Jmjd1a-deficient mice by restoring Sry expression. The administration of a chemical inhibitor of GLP/G9a enzyme into Jmjd1a-deficient embryos also successfully rescued sex reversal. Our study not only reveals the molecular mechanism underlying the tuning of Sry expression but also provides proof on the principle of therapeutic strategies based on the pharmacological modulation of epigenetic balance

Intake of Radionuclides in the Trees of Fukushima Forests 4. Binding of Radioiodine to Xyloglucan

The 1, 4-linked glucans such as xyloglucan and amylose are known to form a complex with iodine/iodide ions and to also be precipitated with CaCl2 in the presence of iodine. Here, we show that iodine gas could be specifically incorporated into xyloglucan. Furthermore, we show that [125I]I2 gas is, over time, incorporated at high levels into the entire outer surface of poplar seedlings but that spraying seedlings with abscisic acid to close stomata decreases the incorporation of the gas. There was less incorporation of the gas in a transgenic poplar overexpressing xyloglucanase at the early stages when compared with a wild type. This shows that xyloglucan serves as a key absorber of iodine gas into a plant body. After individual leaves of cultured seedlings were exposed to the gas for 30 min, no radioiodine was emitted from those leaves over the following two weeks, indicating that no turnover occurs in radioiodine once it is bound to the polysaccharides in plant tissues. We conclude that forest trees could serve as one of the largest enormous capture systems for the radioiodine fallout following the nuclear power plant accident in Fukushima

ナガノケン サン リンゴ カジツ ニ オケル コウサンカノウ ノ ヒンシュカンサイ ト シュウカクビ オヨビ チョゾウ ニ ヨル ヘンカ

長野県で収穫されたリンゴ果実の抗酸化能をoxygen radical absorbance capacity（ORAC）法により測定した。まず6品種の果肉のORAC値を比較した。‘ふじ’については，同日収穫での品質のばらつき，さらに収穫日や貯蔵条件がORAC値に与える影響を調査した。その結果，リンゴのORAC値は‘紅玉’，‘ふじ’が最も高く，‘シナノゴールド’の1.8倍を示した。同日に収穫した果実でも果実間で1.7倍の差異がみられ，ORAC値がばらつきやすい品質であることがわかった。また，暦日から判断した適期で収穫した果実で最も高いORAC値を示したことから，抗酸化能の面からも適期収穫果が高品質であることが示唆された。貯蔵期間中のORAC値は貯蔵温湿度に関わらずほぼ一定であった。抗酸化能の高い果実の提供のためには，収穫時点でのORAC値が高いことが重要だと考えられる。The antioxidant capacity of apples harvested in Nagano prefecture was determined using the oxygen radical absorbance capacity （ORAC） method. We measured the ORAC value of six varieties of apple. The effects of harvest date and storage conditions on ORAC value were also investigated in ‘Fuji’. We found that the ORAC value of ‘Kogyoku’ and ‘Fuji’ was the highest out of the six apple cultivars and 1.8 times higher than that of ‘Shinano Gold’. There was 1.7 times difference in ORAC value between individual fruits of ‘Fuji’. The fruits harvested at the optimum time had the highest ORAC value in ‘Fuji’ apples and the value remained stable during storage. The optimum harvest date determined using the calendar and from experience was also optimal in terms of antioxidant capacity

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target