Identification of tissue-specific cis-regulatory modules based on interactions between transcription factors

<p>Abstract</p> <p>Background</p> <p>Evolutionary conservation has been used successfully to help identify cis-acting DNA regions that are important in regulating tissue-specific gene expression. Motivated by increasing evidence that some DNA regulatory regions are not evolutionary conserved, we have developed an approach for cis-regulatory region identification that does not rely upon evolutionary sequence conservation.</p> <p>Results</p> <p>The conservation-independent approach is based on an empirical potential energy between interacting transcription factors (TFs). In this analysis, the potential energy is defined as a function of the number of TF interactions in a genomic region and the strength of the interactions. By identifying sets of interacting TFs, the analysis locates regions enriched with the binding sites of these interacting TFs. We applied this approach to 30 human tissues and identified 6232 putative cis-regulatory modules (CRMs) regulating 2130 tissue-specific genes. Interestingly, some genes appear to be regulated by different CRMs in different tissues. Known regulatory regions are highly enriched in our predicted CRMs. In addition, DNase I hypersensitive sites, which tend to be associated with active regulatory regions, significantly overlap with the predicted CRMs, but not with more conserved regions. We also find that conserved and non-conserved CRMs regulate distinct gene groups. Conserved CRMs control more essential genes and genes involved in fundamental cellular activities such as transcription. In contrast, non-conserved CRMs, in general, regulate more non-essential genes, such as genes related to neural activity.</p> <p>Conclusion</p> <p>These results demonstrate that identifying relevant sets of binding motifs can help in the mapping of DNA regulatory regions, and suggest that non-conserved CRMs play an important role in gene regulation.</p

Analysis of regulatory network topology reveals functionally distinct classes of microRNAs

MicroRNAs (miRNAs) negatively regulate the expression of target genes at the post-transcriptional level. Little is known about the crosstalk between miRNAs and transcription factors (TFs). Here we provide data suggesting that the interaction patterns between TFs and miRNAs can influence the biological functions of miRNAs. From this global survey, we find that a regulated feedback loop, in which two TFs regulate each other and one miRNA regulates both of the factors, is the most significantly overrepresented network motif. Mathematical modeling shows that the miRNA in this motif stabilizes the feedback loop to resist environmental perturbation, providing one mechanism to explain the robustness of developmental programs that is contributed by miRNAs. Furthermore, on the basis of a network motif profile analysis, we demonstrate the existence of two classes of miRNAs with distinct network topological properties. The first class of miRNAs is regulated by a large number of TFs, whereas the second is regulated by only a few TFs. The differential expression level of the two classes of miRNAs in embryonic developmental stages versus adult tissues suggests that the two classes may have fundamentally different biological functions. Our results demonstrate that the TFs and miRNAs extensively interact with each other and the biological functions of miRNAs may be wired in the regulatory network topology

Genome-wide prediction and characterization of interactions between transcription factors in Saccharomyces cerevisiae

Combinatorial regulation by transcription factor complexes is an important feature of eukaryotic gene regulation. Here, we propose a new method for identification of interactions between transcription factors (TFs) that relies on the relationship of their binding sites, and we test it using Saccharomyces cerevisiae as a model system. The algorithm predicts interacting TF pairs based on the co-occurrence of their binding motifs and the distance between the motifs in promoter sequences. This allows investigation of interactions between TFs without known binding motifs or expression data. With this approach, 300 significant interactions involving 77 TFs were identified. These included more than 70% of the known protein–protein interactions. Approximately half of the detected interacting motif pairs showed strong preferences for particular distances and orientations in the promoter sequences. These one dimensional features may reflect constraints on allowable spatial arrangements for protein–protein interactions. Evidence for biological relevance of the observed characteristic distances is provided by the finding that target genes with the same characteristic distances show significantly higher co-expression than those without preferred distances. Furthermore, the observed interactions were dynamic: most of the TF pairs were not constitutively active, but rather showed variable activity depending on the physiological condition of the cells. Interestingly, some TF pairs active in multiple conditions showed preferences for different distances and orientations depending on the condition. Our prediction and characterization of TF interactions may help to understand the transcriptional regulatory networks in eukaryotic systems

Artificial Synthesis of Conserved Segment S Gene Fragment of Rift Valley Fever Virus and Preliminary Study of Its Reverse Transcription Loop-Mediated Isothermal Amplification Detection Method

Purpose: To develop a rapid detection method for Rift Valley fever virus (RVFV) diagnosis.Methods: According to the reference sequences of RVFV published in GenBank, nine overlapping polymerase chain reaction (PCR) primers and four specific reverse transcription loop-mediated isothermal amplification (RT-LAMP) primers were designed using DNAStar and LAMP primer design software, respectively. Based on the synthesis of a conserved part of the RVFV S segment gene sequence using overlapping PCR, RT-LAMP assay was first established and evaluated after a series of tests, including, optimization of reaction conditions, and sensitivity and specificity tests.Result: A target RVFV S segment gene fragment of 288 bp was synthesised. The optimal reaction conditions for RT-LAMP assay were 63 °C for 45 min: the assay has a specific ladder-like pattern of amplification bands from about 120 bp. The lowest target gene copy number of RT-LAMP for RVFV detection was 70 copies. The assay showed good specificity as only the synthesised target RVFV gene was amplified with no amplification for the detection of Peste des petits ruminants virus, Epidemic encephalitis B virus, E. coli, Pasteurella multocida, or Salmonella.Conclusion: This study provides a rapid, sensitive, specific RT-LAMP method for RVFV detection.Keywords: Rift valley fever virus, Overlapping polymerase chain reaction, Reverse transcription loopmediated isothermal amplification, Rapid diagnosis tes

Proteomic Analysis of Ubiquitinated Proteins in Rice (\u3ci\u3eOryza sativa\u3c/i\u3e) After Treatment With Pathogen-Associated Molecular Pattern (PAMP) Elicitors

Reversible protein ubiquitination plays essential roles in regulating cellular processes. Although many reports have described the functions of ubiquitination in plant defense responses, few have focused on global changes in the ubiquitome. To better understand the regulatory roles of ubiquitination in rice pattern-triggered immunity (PTI), we investigated the ubiquitome of rice seedlings after treatment with two pathogen-associated molecular patterns, the fungal-derived chitin or the bacterialderived flg22, using label-free quantitative proteomics. In chitin-treated samples, 144 and 167 lysine-ubiquitination sites in 121 and 162 proteins showed increased and decreased ubiquitination, respectively. In flg22-treated samples, 151 and 179 lysine-ubiquitination sites in 118 and 166 proteins showed increased and decreased ubiquitination, respectively. Bioinformatic analyses indicated diverse regulatory roles of these proteins. The ubiquitination levels of many proteins involved in the ubiquitination system, protein transportation, ligand recognition, membrane trafficking, and redox reactions were significantly changed in response to the elicitor treatments. Notably, the ubiquitination levels of many enzymes in the phenylpropanoid metabolic pathway were up-regulated, indicating that this pathway is tightly regulated by ubiquitination during rice PTI. Additionally, the ubiquitination levels of some key components in plant hormone signaling pathways were up- or down-regulated, suggesting that ubiquitination may fine-tune hormone pathways for defense responses. Our results demonstrated that ubiquitination, by targeting a wide range of proteins for degradation or stabilization, has a widespread role in modulating PTI in rice. The large pool of ubiquitination targets will serve as a valuable resource for understanding how the ubiquitination system regulates defense responses to pathogen attack

Clay mineralogy indicates a mildly warm and humid living environment for the Miocene hominoid from the Zhaotong Basin, Yunnan, China

Global and regional environmental changes have influenced the evolutionary processes of hominoid primates, particularly during the Miocene. Recently, a new Lufengpithecus cf. lufengensis hominoid fossil with a late Miocene age of ~6.2 Ma was discovered in the Shuitangba (STB) section of the Zhaotong Basin in Yunnan on the southeast margin of the Tibetan Plateau. To understand the relationship between paleoclimate and hominoid evolution, we have studied sedimentary, clay mineralogy and geochemical proxies for the late Miocene STB section (~16 m thick; ca. 6.7–6.0 Ma). Our results show that Lufengpithecus cf. lufengensis lived in a mildly warm and humid climate in a lacustrine or swamp environment. Comparing mid to late Miocene records from hominoid sites in Yunnan, Siwalik in Pakistan, and tropical Africa we find that ecological shifts from forest to grassland in Siwalik are much later than in tropical Africa, consistent with the disappearance of hominoid fossils. However, no significant vegetation changes are found in Yunnan during the late Miocene, which we suggest is the result of uplift of the Tibetan plateau combined with the Asian monsoon geographically and climatically isolating these regions. The resultant warm and humid conditions in southeastern China offered an important refuge for Miocene hominoids

Ferroptosis and hepatocellular carcinoma: the emerging role of lncRNAs

Hepatocellular carcinoma is the most common form of primary liver cancer and poses a significant challenge to the medical community because of its high mortality rate. In recent years, ferroptosis, a unique form of cell death, has garnered widespread attention. Ferroptosis, which is characterized by iron-dependent lipid peroxidation and mitochondrial alterations, is closely associated with the pathological processes of various diseases, including hepatocellular carcinoma. Long non-coding RNAs (lncRNAs), are a type of functional RNA, and play crucial regulatory roles in a variety of biological processes. In this manuscript, we review the regulatory roles of lncRNAs in the key aspects of ferroptosis, and summarize the research progress on ferroptosis-related lncRNAs in hepatocellular carcinoma

Comparative Analysis of Sensory Evaluation Methods for Qingzhuan Tea

To propose a sensory evaluation method suitable for Qingzhuan tea, a representative Qingzhuan tea produced in Hubei was soak or spray boiled in order to analyze the effects of different boiling conditions on the sensory quality and the leaching rate of major chemical components of Qingzhuan tea. The sensory quality and chemical components of the tea infusions were compared with those of tea infusion obtained by the brewing method specified in the Chinese national standard. The results showed that the sensory quality of the boiled tea infusion was significantly better than that of the brewed tea infusion; the leaching rates of major quality components such as water extract, tea polyphenols, amino acids, soluble sugars and tea pigments were much higher in the former than in the latter. From the perspectives of sensory quality and the leaching rate of major quality components, tea infusion prepared by boiling for 2 min with a tea/water ratio of 1:80 and then standing for 2–4 min tasted moderate and had good internal quality. Further correlation analysis showed high correlation coefficients between the leaching rates of soluble sugars, theabrownine and water extract and taste quality. The results of this study provide a reference for the objective evaluation of the sensory quality of Qingzhuan tea and other types of compressed tea

Understanding the relationship between HCV infection and progression of kidney disease

Hepatitis C virus (HCV) can cause a range of kidney diseases. HCV is the primary cause of mixed cryoglobulinaemia, which leads to cryoglobulinaemic vasculitis and cryoglobulinaemic glomerulonephritis (GN). Patients with acute cryoglobulinaemic vasculitis often exhibit acute kidney disease due to HCV infection, which typically progresses to acute kidney injury (AKI). HCV also increases the risk of chronic kidney disease (CKD) and the likelihood of developing end-stage renal disease (ESRD). Currently, direct-acting antiviral agents (DAAs) can be used to treat kidney disease at different stages. This review focuses on key findings regarding HCV and kidney disease, discusses the impact of DAAs, and highlights the need for further research and treatment

Clinical and Epidemiologic Research Prevalence of and Risk Factors for Pterygium in Rural Adult Chinese Populations of the Bai Nationality in Dali: The Yunnan Minority Eye Study

PURPOSE. The purpose of the study was to describe the prevalence, severity, and associated risk factors for pterygium in a population-based sample of rural residents of the Bai minority population in rural Dali, China. METHODS. A population-based survey of Chinese Bai Nationality aged ‡50 years from randomly selected block groups in southwestern China was conducted. A clinical examination by experienced ophthalmologists was carried out, and the presence of pterygium was diagnosed at the examination. Pterygium was graded clinically by slit lamp examination. Questionnaires were conducted on risk factors. RESULTS. From a total of 2742 eligible subjects, 2133 (77.8%) were examined. CONCLUSIONS. The prevalence of pterygium in Dali is 39.0% among Chinese Bai aged 50 years and older. Independent associations with increasing age (&gt;59 years), female sex, lack of education, and occupations linked to outdoor work suggest a multifactorial cause of this condition. (Invest Ophthalmol Vis Sci. 2012;53:6617-6621