Genomic Regions Flanking E-Box Binding Sites Influence DNA Binding Specificity of bHLH Transcription Factors through DNA Shape

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Highlights? Cbf1 and Tye7 are paralogous TFs with virtually identical DNA binding-site motifs ? The two paralogous TFs bind different genomic target sites in vivo ? The genomic context of putative DNA binding sites affects TF binding specificity ? Structural analyses suggest that genomic context influences TF binding through DNA shape     

Impact of Protein/Protein Interactions on Global Intermolecular Translocation Rates of the Transcription Factors Sox2 and Oct1 between DNA Cognate Sites Analyzed by z-Exchange NMR Spectroscopy

Oct1 and Sox2 synergistically regulate developmental genes by binding to adjacent sites within promoters. We have investigated the kinetics of global intermolecular translocation of Sox2 and Oct1 between cognate sites located on different DNA molecules by z-exchange NMR spectroscopy. In the Hoxb1 promoter, the Sox2 and Oct1 sites are immediately adjacent to one another, and the intermolecular translocation rates are too slow to be measured by z-exchange spectroscopy. By introducing a 3-bp insertion between the Sox2 and Oct1 sites to mimic the spacing in the FGF4 enhancer, the interprotein contact surface is reduced, and the translocation rates are increased. Interaction between Sox2 and the POU-specific domain (POU(S)) of Oct1 does not affect the translocation mechanism but modulates the rates. Translocation involves only jumping (dissociation and reassociation) for Sox2, but both jumping and direct intersegment transfer (no dissociation into free solution) for Oct1. The dissociation (k(off) ～1.5 s(-1)) and association (k(on) ～5.1 × 10(9) m(-1)s(-1)) rate constants for Sox2 are reduced 4-fold and increased 5-fold, respectively, in the presence of Oct1. k(off) (～3.5 s(-1)) for Oct1 is unaffected by Sox2, whereas k(on) (～1.3 × 10(9) m(-1)s(-1)) is increased ～13-fold. The direct intermolecular translocation rate (k(inter) ～1.8 × 10(4) m(-1)s(-1)) for the POU(S) domain of Oct1 is reduced 2-fold by Sox2, whereas that for the POU homeodomain (POU(HD)) of Oct1 (k(inter) ～ 1.7 × 10(4) m(-1)s(-1)) remains unaltered, consistent with the absence of contacts between Sox2 and POU(HD). The data suggest a model for the sequence of binding events involved in synergistic gene regulation by Sox2 and Oct1.     

植物对非生物胁迫应答的转录因子及调控机制

植物对非生物胁迫的应答反应涉及到许多基因和生化分子机制,胁迫相关基因、蛋白质及代谢物构成了一个复杂的调控网络,其中转录控制具有举足轻重的作用。本文主要对近年来发现的几种在转录控制中起关键作用的转录因子CBF/DREB、bZIP、MYB/MYC和HSF及其调控机制进行介绍。这几种转录因子可以分别和胁迫应答顺式作用元件CRT/DRE、ABRE、MYB/MYC识别位点及HSE结合,在非生物胁迫条件下调控下游靶基因的表达,进而使一些胁迫保护物质如脯氨酸、可溶性糖类、自由基的清除剂、热休克蛋白和分子伴侣等的表达水平升高,最终增强植物对非生物胁迫的耐受能力。     

iTAG-RNA Isolates Cell-Specific Transcriptional Responses to Environmental Stimuli and Identifies an RNA-Based Endocrine Axis

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Interactions between Exposure to Environmental Polycyclic Aromatic Hydrocarbons and DNA Repair Gene Polymorphisms on Bulky DNA Adducts in Human Sperm

Background

Nucleotide excision repair (NER) and base excision repair (BER) are the primary mechanisms for repair of bulky adducts caused by chemical agents, such as PAHs. It is expected that polymorphisms in NER or BER genes may modulate individual susceptibility to PAHs exposure. Here, we evaluate the effects of PAHs exposure and polymorphisms in NER and BER pathway, alone or combined, on polycyclic aromatic hydrocarbon-DNA (PAH–DNA) adducts in human sperm.

Methodology/Principal Findings

Sperm PAH-DNA adducts were measured by immunofluorescent assay using flow cytometry in a sample of 465 infertile adults. Polymorphisms of XPA, XPD, ERCC1, XPF, and XRCC1 were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. The PAHs exposure was detected as urinary 1-hydroxypyrene (1-OHP) levels. In multivariate models adjusted for potential confounders, we observed that XRCC1 5′pUTR -T/C, Arg194Trp, Arg399Gln polymorphisms were associated with increased sperm adduct levels. Furthermore, the stratified analysis indicated that adverse effects of XRCC1 Arg194Trp, Arg399Gln polymorphisms on PAH-DNA adducts were detected only in the high PAHs exposure group.

Conclusions/Significance

These findings provided the first evidence that polymorphisms of XRCC1 may modify sperm PAH-DNA adduct levels and may be useful biomarkers to identify individuals susceptible to DNA damage resulting from PAHs exposure.     

Prediction of Disease-Related Interactions between MicroRNAs and Environmental Factors Based on a Semi-Supervised Classifier

Accumulated evidence has shown that microRNAs (miRNAs) can functionally interact with a number of environmental factors (EFs) and their interactions critically affect phenotypes and diseases. Therefore, in-silico inference of disease-related miRNA-EF interactions is becoming crucial not only for the understanding of the mechanisms by which miRNAs and EFs contribute to disease, but also for disease diagnosis, treatment, and prognosis. In this paper, we analyzed the human miRNA-EF interaction data and revealed that miRNAs (EFs) with similar functions tend to interact with similar EFs (miRNAs) in the context of a given disease, which suggests a potential way to expand the current relation space of miRNAs, EFs, and diseases. Based on this observation, we further proposed a semi-supervised classifier based method (miREFScan) to predict novel disease-related interactions between miRNAs and EFs. As a result, the leave-one-out cross validation has shown that miREFScan obtained an AUC of 0.9564, indicating that miREFScan has a reliable performance. Moreover, we applied miREFScan to predict acute promyelocytic leukemia-related miRNA-EF interactions. The result shows that forty-nine of the top 1% predictions have been confirmed by experimental literature. In addition, using miREFScan we predicted and publicly released novel miRNA-EF interactions for 97 human diseases. Finally, we believe that miREFScan would be a useful bioinformatic resource for the research about the relationships among miRNAs, EFs, and human diseases.     

Interactions between Environmental Factors and Melatonin Receptor Type 1A Polymorphism in Relation to Oral Cancer Susceptibility and Clinicopathologic Development

Background

The purpose of this study was to explore the combined effect of melatonin receptor type 1A (MTNR1A) gene polymorphisms and exposure to environmental carcinogens on the susceptibility and clinicopathological characteristics of oral cancer.

Methodology and Principal Findings

Three polymorphisms of the MTNR1A gene from 618 patients with oral cancer and 560 non-cancer controls were analyzed by real-time polymerase chain reaction (PCR). The CTA haplotype of the studied MTNR1A polymorphisms (rs2119882, rs13140012, rs6553010) was related to a higher risk of oral cancer. Moreover, MTNR1A gene polymorphisms exhibited synergistic effects of environmental factors (betel quid and tobacco use) on the susceptibility of oral cancer. Finally, oral-cancer patients with betel quid-chewing habit who had T/T allele of MTNR1A rs13140012 were at higher risk for developing an advanced clinical stage and lymph node metastasis.

Conclusion

These results support gene-environment interactions of MTNR1A polymorphisms with smoking and betel quid-chewing habits possibly altering oral-cancer susceptibility and metastasis.     

DREB转录因子及其在植物抗逆中的作用

介绍了DREB(dehydration responsive element binding)转录因子及其在植物抗逆作用中的研究进展.DREB转录因子由逆环境胁迫诱导产生后,可激活其他多达12个依赖DRE顺式作用元件的抗逆功能基因,引起脯氨酸及蔗糖含量提高,从而增强植株对多种逆境(旱、冻及盐)的抵抗性.