Tn5 tagments and transposes oligos to single-stranded DNA for strand-specific RNA sequencing.

Tn5 transposon tagments double-stranded DNA and RNA/DNA hybrids to generate nucleic acids that are ready to be amplified for high-throughput sequencing. The nucleic acid substrates for the Tn5 transposon must be explored to increase the applications of Tn5. Here, we found that the Tn5 transposon can transpose oligos into the 5' end of single-stranded DNA longer than 140 nucleotides. Based on this property of Tn5, we developed a tagmentation-based and ligation-enabled single-stranded DNA sequencing method called TABLE-seq. Through a series of reaction temperature, time, and enzyme concentration tests, we applied TABLE-seq to strand-specific RNA sequencing, starting with as little as 30 pg of total RNA. Moreover, compared with traditional dUTP-based strand-specific RNA sequencing, this method detects more genes, has a higher strand specificity, and shows more evenly distributed reads across genes. Together, our results provide insights into the properties of Tn5 transposons and expand the applications of Tn5 in cutting-edge sequencing techniques.

The H3K36me2 methyltransferase NSD1 modulates H3K27ac at active enhancers to safeguard gene expression.

Epigenetics, especially histone marks, functions beyond the DNA sequences to regulate gene expression. Depletion of NSD1, which catalyzes H3K36me2, leads to both up- and down-regulation of gene expression, indicating NSD1 is associated with both active and repressed gene expression. It's known that NSD1 regulates the deposition and expansion of H3K27me3, a repressive mark for gene expression, to keep active gene transcription. However, how NSD1 functions to repress gene expression is largely unknown. Here, we find that, when NSD1 is knocked out in mouse embryonic stem cells (mESCs), H3K27ac increases correlatively with the decrease of H3K36me2 at active enhancers, which is associated with mesoderm differentiation genes, leading to elevated gene expression. Mechanistically, NSD1 recruits HDAC1, the deacetylase of H3K27ac, to chromatin. Moreover, HDAC1 knockout (KO) recapitulates the increase of H3K27ac at active enhancers as the NSD1 depletion. Together, we propose that NSD1 deposits H3K36me2 and recruits HDAC1 at active enhancers to serve as a 'safeguard', preventing further activation of active enhancer-associated genes.

Overview of Histone Modification.

Epigenetics is the epi-information beyond the DNA sequence that can be inherited from parents to offspring. From years of studies, people have found that histone modifications, DNA methylation, and RNA-based mechanism are the main means of epigenetic control. In this chapter, we will focus on the general introductions of epigenetics, which is important in the regulation of chromatin structure and gene expression. With the development and expansion of high-throughput sequencing, various mutations of epigenetic regulators have been identified and proven to be the drivers of tumorigenesis. Epigenetic alterations are used to diagnose individual patients more accurately and specifically. Several drugs, which are targeting epigenetic changes, have been developed to treat patients regarding the awareness of precision medicine. Emerging researches are connecting the epigenetics and cancers together in the molecular mechanism exploration and the development of druggable targets.

Healthier Dietary Patterns Are Associated with Better Sleep Quality among Shanghai Suburban Adults: A Cross-Sectional Study.

BACKGROUND: More is to be explored between dietary patterns and sleep quality in the Chinese adult population. METHODS: A cross-sectional study including 7987 Shanghai suburban adults aged 20-74 years was conducted. Dietary information was obtained using a validated food frequency questionnaire. Adherence to a priori dietary patterns, such as the Chinese Healthy Eating Index (CHEI), Dietary Approaches to Stop Hypertension (DASH) diet and Mediterranean diet (MD), was assessed. Sleep quality was assessed from self-reported responses to the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Logistic regression models adjusting for confounders were employed to examine the associations. RESULTS: The overall prevalence of poor sleep (PSQI score ≥ 5) was 28.46%. Factor analysis demonstrated four a posteriori dietary patterns. Participants with a higher CHEI (ORQ4 vs. Q1: 0.81, 95% CI: 0.70-0.95), DASH (ORQ4 vs. Q1: 0.70, 95% CI: 0.60-0.82) or MD (ORQ4 vs. Q1: 0.75, 95% CI: 0.64-0.87) had a lower poor sleep prevalence, while participants with a higher "Beverages" score had a higher poor sleep prevalence (ORQ4 vs. Q1: 1.18, 95% CI: 1.02-1.27). CONCLUSIONS: In Shanghai suburban adults, healthier dietary patterns and lower consumption of beverages were associated with better sleep quality.

Association of Serum Uric Acid with Diabetes in Premenopausal and Postmenopausal Women-A Prospective Cohort Study in Shanghai, China.

There have been few prospective studies on the association between serum uric acid (SUA) and the risk of diabetes in women, and there have been few large-scale Chinese studies based on menopause to investigate the association. Therefore, the present study aimed to investigate the above relationship in Chinese female adults without diabetes. Methods: Data from 5743 premenopausal women and 11,287 postmenopausal women aged 20−74 years were obtained from the Shanghai Suburban Adult Cohort and Biobank (SSACB) study conducted in China. Cox regression models were applied to evaluate the association between SUA levels and the risk of diabetes. Restricted cubic spline analysis and stratified analysis on the basis of menopausal status were performed to explore the dose−response association between SUA levels and diabetes. Results: Among 17,030 participants, incidence rates of diabetes were 3.44/1000 person-years in premenopausal and 8.90/1000 person-years in postmenopausal women. The SUA levels in postmenopausal women were higher than that in premenopausal women (p < 0.0001). In Cox regression analysis, after adjusting for confounding factors, for each 10 µmol/L increase in SUA levels, the adjusted HR of diabetes was 1.01 (95% CI: 0.97−1.04) in postmenopausal women, and 1.03 (95% CI: 1.01−1.04) in premenopausal women. Compared with the lowest quartile of SUA levels, the HR (95% CI) of diabetes in the highest quartile was 0.99 (0.55−1.79) in premenopausal women and 1.39 (1.07−1.81) in postmenopausal women. Compared with those without hyperuricemia, the HR (95% CI) for diabetes was 1.89 (0.67−5.31) in premenopausal women with hyperuricemia, and 1.55 (1.19−2.02) in postmenopausal women. Moreover, restricted cubic splines models showed that there was a linear relationship between SUA levels and diabetes risk in premenopausal (p for nonlinear = 0.99) and postmenopausal women (p for nonlinear = 0.95). Furthermore, the restricted cubic spline graph showed that the risk of diabetes in postmenopausal women increased with an increase in SUA levels (p = 0.002). Conclusions: In a cohort of Chinese adult women, SUA levels are associated with diabetes risk in postmenopausal women, but this association was not observed in premenopausal women.

Joint single-cell multiomic analysis in Wnt3a induced asymmetric stem cell division.

Wnt signaling usually functions through a spatial gradient. Localized Wnt3a signaling can induce the asymmetric division of mouse embryonic stem cells, where proximal daughter cells maintain self-renewal and distal daughter cells acquire hallmarks of differentiation. Here, we develop an approach, same cell epigenome and transcriptome sequencing, to jointly profile the epigenome and transcriptome in the same single cell. Utilizing this method, we profiled H3K27me3 and H3K4me3 levels along with gene expression in mouse embryonic stem cells with localized Wnt3a signaling, revealing the cell type-specific maps of the epigenome and transcriptome in divided daughter cells. H3K27me3, but not H3K4me3, is correlated with gene expression changes during asymmetric cell division. Furthermore, cell clusters identified by H3K27me3 recapitulate the corresponding clusters defined by gene expression. Our study provides a convenient method to jointly profile the epigenome and transcriptome in the same cell and reveals mechanistic insights into the gene regulatory programs that maintain and reset stem cell fate during differentiation.

H3K36me3, message from chromatin to DNA damage repair.

Histone marks control many cellular processes including DNA damage repair. This review will focus primarily on the active histone mark H3K36me3 in the regulation of DNA damage repair and the maintenance of genomic stability after DNA damage. There are diverse clues showing H3K36me3 participates in DNA damage response by directly recruiting DNA repair machinery to set the chromatin at a "ready" status, leading to a quick response upon damage. Reduced H3K36me3 is associated with low DNA repair efficiency. This review will also place a main emphasis on the H3K36me3-mediated DNA damage repair in the tumorigenesis of the newly found oncohistone mutant tumors. Gaining an understanding of different aspects of H3K36me3 in DNA damage repair, especially in cancers, would share the knowledge of chromatin and DNA repair to serve to the drug discovery and patient care.