Complementary Alu sequences mediate enhancer-promoter selectivity.

Enhancers determine spatiotemporal gene expression programs by engaging with long-range promoters1-4. However, it remains unknown how enhancers find their cognate promoters. We recently developed a RNA in situ conformation sequencing technology to identify enhancer-promoter connectivity using pairwise interacting enhancer RNAs and promoter-derived noncoding RNAs5,6. Here we apply this technology to generate high-confidence enhancer-promoter RNA interaction maps in six additional cell lines. Using these maps, we discover that 37.9% of the enhancer-promoter RNA interaction sites are overlapped with Alu sequences. These pairwise interacting Alu and non-Alu RNA sequences tend to be complementary and potentially form duplexes. Knockout of Alu elements compromises enhancer-promoter looping, whereas Alu insertion or CRISPR-dCasRx-mediated Alu tethering to unregulated promoter RNAs can create new loops to homologous enhancers. Mapping 535,404 noncoding risk variants back to the enhancer-promoter RNA interaction maps enabled us to construct variant-to-function maps for interpreting their molecular functions, including 15,318 deletions or insertions in 11,677 Alu elements that affect 6,497 protein-coding genes. We further demonstrate that polymorphic Alu insertion at the PTK2 enhancer can promote tumorigenesis. Our study uncovers a principle for determining enhancer-promoter pairing specificity and provides a framework to link noncoding risk variants to their molecular functions.

The Landscape of Early Growth Response Family Members 1-4 in Hepatocellular Carcinoma: Their Biological Roles and Diagnostic Utility.

The incidence of hepatocellular carcinoma (HCC), which is one of the most frequent types of cancer seen all over the world, is steadily growing from year to year. EGR genes are members of the early growth response (EGR) gene family. It has been shown that EGR genes play an increasingly essential role in the development of tumors and the progression of numerous malignancies. However, the possible diagnostic and prognostic roles of EGR genes in HCC have only been examined in a limited number of studies. Expression and methylation data on EGR family members were obtained from TCGA datasets. The prognostic values of EGR members were studied. Additionally, the correlations of EGR members with immune cells were assessed through the single-sample gene set enrichment analysis (ssGSEA). In this study, we found that the expression of EGR1, EGR2, EGR3, and EGR4 was distinctly decreased in HCC specimens compared with nontumor specimens. ROC assays confirmed that they have a strong ability in screening HCC specimens from nontumor specimens. According to the findings of Pearson's correlation, EGR1, EGR2, EGR3, and EGR4 were found to have a negative association with the methylation level. Survival study revealed that EGR1, EGR2, and EGR3 were associated with the clinical outcome of HCC patients. Immune cell enrichment analysis demonstrated that the expressions of all EGR members were positively related to the levels of most types of immune cells, such as macrophages, NK cells, B cells, T cells, eosinophils, and CD8 T cells. Overall, the current work demonstrated the expression mode and prognostic value of EGR members in HCC in a comprehensive manner, offering insights for further research of the EGR family as possible clinical biomarkers in HCC.

Epidemiological Investigation and Prevention Control Analysis of the Longitudinal Distribution of COVID-19 in Henan Province, China.

The objective was to analyze the longitudinal distribution, epidemiological characteristics, and local prevention and control measures of coronavirus disease 2019 (COVID-19) in six cities in Henan Province, China, from 21 January 2020 to 17 June 2020: Xinyang City (including Gushi County), Nanyang City (including Dengzhou City), Zhumadian City (including Xincai County), Zhengzhou City (including Gongyi City), Puyang City, and Anyang City (including Hua County). Data were collected and analyzed through the COVID-19 information published on the official websites of the health commissions in the six selected cities of Henan Province. As of 17 June 2020, the cumulative incidence rate of COVID-19 in Henan Province was 1.33/100,000, the cumulative cure rate was 98.27%, the cumulative mortality rate was 1.73%, the age range of diagnosed cases was 5 days to 85 years old, and the male-to-female ratio was 1.09:1. The confirmed cases of COVID-19 in Henan Province were mainly imported cases from Hubei, accounting for 87.74% of all cases, of which the highest proportion was 70.50% in Zhumadian. The contact cases and local cases increased in a fluctuating manner over time. In this paper, epidemiological characteristics of COVID-19 in Henan Province were analyzed from the onset of the outbreak to the effective control within 60 days, and effective and distinctive prevention and control measures in various cities were summarized to provide a favorable useful reference for the further formulation and implementation of epidemic prevention and control and a valuable theoretical basis for effectively avoiding a second outbreak.IMPORTANCE Epidemic prevention and control in China have entered a new stage of normalization. This article analyzes the epidemiological characteristics of COVID-19 in Henan Province and summarizes the effective disease prevention and control means and measures at the prefecture level; the normalized private data provide a theoretical reference for the formulation and conduct of future prevention and control work. At the same time, these epidemic prevention and control findings can also be used for reference in other countries and regions.