AOF1 is a histone H3K4 demethylase possessing demethylase activity-independent repression function

LSD1 （KDM1 under the new nomenclature） was the first identified lysine-specific histone demethylase belonging to the flavin-dependent amine oxidase family. Here, we report that AOF1 （KDM1B under the new nomenclature）, a mammalian protein related to LSD1, also possesses histone demethylase activity with specificity for H3K4mel and H3K4me2. Like LSD1, the highly conserved SWIRM domain is required for its enzymatic activity. However, AOF1 differs from LSD1 in several aspects. First, AOF1 does not appear to form stable protein complexes containing histone deacetylases. Second, AOF1 is found to localize to chromosomes during the mitotic phase of the cell cycle, whereas LSD1 does not. Third, AOF1 represses transcription when tethered to DNA and this repression activity is independent of its demethylase activity. Structural and functional analyses identified its unique N-terminal Zf-CW domain as essential for the demethylase activity-independent repression function. Collectively, our study identifies AOF1 as the second histone demethylase in the family of flavin-dependent amine oxidases and reveals a demethylase-independent repression function of AOF1.

Repression of interferon-γ expression in T cells by Prosperorelated Homeobox protein

Interferon-gamma （IFN-γ） is a major proinflammatory effector and regulatory cytokine produced by activated T cells and NK cells. IFN-γ has been shown to play pivotal roles in fundamental immunological processes such as inflammatory reactions, cell-mediated immunity and autoimmunity. A variety of human disorders have now been linked to irregular IFN-γ expression. In order to achieve proper IFN-γ-mediated immunological effects, IFN-γ expression in T cells is subject to both positive and negative regulation. In this study, we report for the first time the negative regulation of IFN-γ expression by Prospero-related Homeobox （Proxl）. In Jurkat T cells and primary human CD4＋ T cells, Proxl expression decreases quickly upon T cell activation, concurrent with a dramatic increase in IFN-γ expression. Reporter analysis and chromatin immunoprecipitation （CHIP） revealed that Proxl associates with and inhibits the transcription activity of IFN-γ promoter in activated Jurkat T cells. Co-immunoprecipitation and GST pull-down assay demonstrated a direct binding between Proxl and the nuclear receptor peroxisome proliferator-activated receptor gamma （PPARγ）, which is also an IFN-γ repressor in T cells. By introducing deletions and mutations into Proxl, we show that the repression of IFN-γ promoter by Proxl is largely dependent upon the physical interaction between Proxl and PPARγ. Furthermore, PPARγ antagonist treatment removes Proxl from IFN-γ promoter and attenuates repression of IFN-γ expression by Proxl. These findings establish Proxl as a new negative regulator of IFN-γ expression in T cells and will aid in the understanding of IFN-γ transcription regulation mechanisms.

Inhibition of SIRT1 Increases EZH2 Protein Level and Enhances the Repression of EZH2 on Target Gene Expression

Objective To study the regulatory roles of SIRT1 on EZH2 expression and the further ef-fects on EZH2's repression of target gene expression. Methods The stable SIRT1 RNAi and Control RNAi HeLa cells were established by in-fection with retroviruses expressing shSIRT1 and shLuc respectively followed by puromycin selection. EZH2 protein level was detected by Western blot in either whole cell lysate or the fractional cell extract. Reverse transcription-polymerase chain reaction was performed to detect the mRNA level of EZH2. Cycloheximide was used to treat SIRT1 RNAi and Control RNAi cells for protein stability assay. Chromatin immunoprecipitation (ChIP) assay was applied to measure enrichment of SIRT1, EZH2, and trimethylated H3K27 (H3K27me3) at SATB1 promoter in SIRT1 RNAi and Control RNAi cells. Results Western blot results showed that EZH2 protein level increased upon SIRT1 de-pletion. Fractional extraction results showed unchanged cytoplasmic fraction and increased chromatin fraction of EZH2 protein in SIRT1 RNAi cells. The mRNA level of EZH2 was not affected by knockdown of SIRT1. SIRT1 recruitment was not detected at the promoter region of EZH2 gene locus. The protein stability assay showed that the protein stability of EZH2 increases upon SIRT1 knockdown. Upon SIRT1 depletion, EZH2 and H3K27me3 recruitment at SATB1 promoter increases and the mRNA level of SATB1 decreases. Conclusions Depletion of SIRT1 increases the protein stability of EZH2. The regulation of EZH2 protein level by SIRT1 affects the repressive effects of EZH2 on the target gene expres-sion.

Women＇s repression, rebellion and quest for the ＂true self＂： Theyellow wallpaper as the epitome of the female Gothic novel

As a genre that expressed women＇s dark protests, fantasies and the fear, female Gothic was not theorized until the late 1960s, and before its theorization, this convention was adopted by many women writers in their works. Charlotte Perkins Gilman＇s The yellow wallpaper is one of the many examples. As the epitome of female gothic, The yellow wallpaper utilized the female gothic conventions--the grotesque symbol of yellow wallpaper, the hysteric narrative format and the archetype image of madwoman, to express women＇s status of her time--their repression, rebellion and quest for the ＂true self＂.

Empirical study on the financial repression of rural households＇ debit and credit and the effects on their welfare in less developed regions --Take Suqian city of Jiangsu province as an example

This paper carries out empirical analysis of the ration behavior of rural credit cooperatives in less developed regions in providing loan services to rural households. It also inspects the interaction between rural households＇ demand for credit and the loan supply from rural credit cooperatives with simultaneous discrete model. The performance of supporting agriculture through a new round reform of rural credit cooperatives is doubtable in this sample region.

An Updated GA Signaling ＇Relief of Repression＇ Regulatory Model

Gibberellic acid （GA） regulates many aspects of plant growth and development. The DELLA proteins act to restrain plant growth, and GA relieves this repression by promoting their degradation via the 26S proteasome pathway. The elucidation of the crystalline structure of the GA soluble receptor GID1 protein represents an important breakthrough for understanding the way in which GA is perceived and how it induces the destabilization of the DELLA proteins. Recent advances have revealed that the DELLA proteins are involved in protein-protein interactions within various environmental and hormone signaling pathways. In this review, we highlight our current understanding of the ＇relief of repression＇ model that aims to explain the role of GA and the function of the DELLA proteins, incorporating the many aspects of cross-talk shown to exist in the control of plant development and the response to stress.

Transcriptional Repression by Histone Deacetylases in Plants

Reversible histone acetylation and deacetylation at the N-terminus of histone tails play crucial roles in regulation of eukaryotic gene activity. Acetylation of core histones usually induces an ＇open＇ chromatin structure and is associated with gene activation, whereas deacetylation of histone is often correlated with ＇closed＇ chromatin and gene repression. Histone deacetylation is catalyzed by histone deacetylases （HDACs）. A growing number of studies have demonstrated the importance of histone deacetylation/acetylation on genome stability, transcriptional regulation, and development in plants. Furthermore, HDACs were shown to interact with various chromatin remolding factors and transcription factors involved in transcriptional repression in multiple developmental processes. In this review, we summarized recent findings on the transcriptional repression mediated by HDACs in plants.

China's Exchange Rate and Financial Repression:The Conflicted Emergence of the RMB as an International Currency

Instability in the worm dollar standard, as most recently manifested in the US Federal Reserve＇s near-zero interest rate policy, has caused consternation in emerging markets with naturally higher interest rates. China has been provoked into speeding RMB ＂internationalization ＂; that is, opening up domestic financial markets to reduce its dependence on the US dollar for invoicing trade and making international payments. However, despite rapid percentage growth in offshore financial markets in RMB, the Chinese authorities are essentially trapped into maintaining exchange controls （reinforced by financial repression in domestic interest rates） to avoid an avalanche of foreign capital inflows that would threaten inflation and asset price bubbles by driving nominal interest rates on RMB assets down further. Because a floating （appreciating） exchange rate could attract even more hot money inflows, the People＇s Bank of China should focus on keeping the yuan/dollar rate stable so as to encourage naturally high wage increases to help balance China ＂s international competitiveness. However, further internationalization of the RMB, as with the proposed Shanghai pilot free trade zone, is best deferred until world interest rates rise to more normal levels.

Chinese Stylized Sterilization:The Cost-sharing Mechanism and Financial Repression

This paper attempts to explain why sterilized intervention was so successful and sustainable in China during the first decade of the 21st century. We argue that the Chinese Government established a sterilization cost-sharing mechanism among the Peoples Bank of China, commercial banks and the househoM sector. On the one hand, Chinese commercial banks have to assume some of the sterilization costs bypurchasing low yield central bank bills and maintaining high levels of required reserves. On the other hand, Chinese households assume some of the sterilization costs by bearing negative real deposit interest rates. The cost- sharing mechanism under financial repression prevents a huge quasi-fiscal loss by the Peoples Bank of China as well as high inflation. However, Chinese households have become victims of this financial repression. Faced with the pressure of changing the growth model from investment-driven to domestic consumption-driven, the interest rate will have to be liberalized eventually, which will, in turn, make sterilized intervention unsustainable.

PRCl Marks the Difference in Plant PcG Repression

From mammals to plants, the Polycomb Group （PcG） machinery plays a crucial role in maintaining the repres- sion of genes that are not required in a specific differentiation status. However, the mechanism by which PeG machinery mediates gene repression is still largely unknown in plants. Compared to animals, few PcG proteins have been identi- fied in plants, not only because just some of these proteins are clearly conserved to their animal counterparts, but also because some PcG functions are carried out by plant-specific proteins, most of them as yet uncharacterized. For a long time, the apparent lack of Polycomb Repressive Complex （PRC）I components in plants was interpreted according to the idea that plants, as sessile organisms, do not need a long-term repression, as they must be able to respond rapidly to environmental signals; however, some PRC1 components have been recently identified, indicating that this may not be the case. Furthermore, new data regarding the recruitment of PcG complexes and maintenance of PcG repression in plants have revealed important differences to what has been reported so far. This review highlights recent progress in plant PcG function, focusing on the role of the putative PRC1 components.

Epigenetic Repression of Male Gametophyte- Specific Genes in the Arabidopsis Sporophyte

Tissue formation, the identity of cells, and the functions they fulfill, are results of gene regulation. The male gametophyte of plants, pollen, is outstanding in this respect as several hundred genes expressed in pollen are not expressed in the sporophyte. How pollen-specific genes are down-regulated in the sporophyte has yet to be established. In this study, we have performed a bioinformatics analysis of publicly available genome-wide epigenetics data of sev- eral sporophytic tissues. By combining this analysis with DNase ! footprinting data, we assessed means by which the repression of pollen-specific genes in the Arabidopsis sporophyte is conferred. Our findings show that, in seedlings, the majority of pollen-specific genes are associated with histone-3 marked by mono- or trimethylation of Lys-27 （H3K27me1/ H3K27me3）, both of which are repressive markers for gene expression in the sporophyte. Analysis of DNase footprint profiles of pollen-specific genes in the sporophyte displayed closed chromatin proximal to the start codon. We describe a model of two-staged gene regulation in which a lack of nucleosome-free regions in promoters and histone modifications in open reading frames repress pollen-specific genes in the sporophyte.

Implications of carbon catabolite repression for plant–microbe interactions

Carbon catabolite repression(CCR)plays a key role in many physiological and adaptive responses in a broad range of microorganisms that are commonly associated with eukaryotic hosts.When a mixture of different carbon sources is available,CCR,a global regulatory mechanism,inhibits the expression and activity of cellular processes associated with utilization of secondary carbon sources in the presence of the preferred carbon source.CCR is known to be executed by completely different mechanisms in different bacteria,yeast,and fungi.In addition to regulating catabolic genes,CCR also appears to play a key role in the expression of genes involved in plant–microbe interactions.Here,we present a detailed overview of CCR mechanisms in various bacteria.We highlight the role of CCR in beneficial as well as deleterious plant–microbe interactions based on the available literature.In addition,we explore the global distribution of known regulatory mechanisms within bacterial genomes retrieved from public repositories and within metatranscriptomes obtained from different plant rhizospheres.By integrating the available literature and performing targeted meta-analyses,we argue that CCR-regulated substrate use preferences of microorganisms should be considered an important trait involved in prevailing plant–microbe interactions.

Spatial heterogeneity and host repression in fig-fig wasp mutualism

It is generally believed that physical heterogeneity in common resource or evolutionary restraint can sufficiently prevent direct conflict between host and symbionts in mutualism systems. Our data on fig/fig wasp reciprocal mutualism(Ficus racemosa), however, show that structural barriers of female flowers or genetic constraints of pollinators previously hypothesized exist, but cannot sufficiently maintain the mutualism stability. The results show that a positive relationship between seed and wasp production could be maintained in warm season, which might be because of density dependence restraint among foundresses and their low oviposition and pollination efficiency, keeping common resource(female flowers) utilization unsaturated. Whilst, a negative correlation between wasp offspring and viable seed production was also observed in cold season, which might be that the increased oviposition and pollination efficiency maximized the common resource utilization. The fitness trade-off between fig and pollinator wasps is greatly affected by environmental or ecological variations. The local stability might result from temporal low exploitation efficiency of pollinators together with interference competition among pollinators. We suggest that host repression through the active regulation of bract closure, which can create interference competition among the foundresses and prevent extra more foundresses sequential entry in fruit cavities, would help the figs avoiding the cost of over-exploitation. This essentially takes the same role as sanctioning of cheating or competitive behaviors.

Transcriptional repression of hDaxx enhanced by adenovirus 12 E1B 55-kDa oncoprotein interacting with hDaxx

Background Daxx has been identified as a nuclear protein that involves in apoptosis and transcriptional repression. Daxx co-localizes with the promyelocytic leukemia (PML) protein and regulates transcription. Human Daxx (hDaxx) is a protein that functions as a transcriptional regulation through its interaction with some DNA-associated proteins. The aim of this study was to explore the transcriptional regulatory effect of hDaxx interacting with adenovirus (Ad) 12 E1B (Ad12E1B) 55-kDa oncoprotein Methods The co-localization of hDaxx-Ad12E1B or hDaxx-PML protein in the nucleus was observed under a confocal microscope Interaction of hDaxx and Ad12E1B was analyzed by yeast two-hybrid assay Direct binding of hDaxx and Ad12E1B was analyzed using coimmunoprecipitation and Western blot in vivo and in vitro The activity of a luciferase reporter gene, which was regulated by an hDaxx modulated thymidine kinase (TK) promoter, was detected in an automat luminometer Results Ad12E1B, which co-localized with hDaxx in the nuclei of G401-CC3 cells, disrupted the co-localization of hDaxx and PML in the PML oncogenic domains (PODs) hDaxx bound directly to Ad12E1B in vivo and in vitro hDaxx interacted with Ad12E1B along its full length Ad12E1B enhanced transcriptional repression activity of hDaxx Conclusion Ad12E1B disrupts the co-localization of hDaxx with PML in PODs and enhances transcriptional repression activity of hDaxx

Redesigning transcription factor Cre1 for alleviating carbon catabolite repression in Trichoderma reesei

Carbon catabolite repression(CCR),which is mainly mediated by Cre1 and triggered by glucose,leads to a decrease in cellulase production in Trichoderma reesei.Many studies have focused on modifying Cre1 for alleviating CCR.Based on the homologous alignment of CreA from wild-type Penicillium oxalicum 114–2(Po-0)and cellulase hyperproducer JUA10-1(Po-1),we constructed a C-terminus substitution strain—Po-2—with decreased transcriptional levels of cellulase and enhanced CCR.Results revealed that the C-terminal domain of CreAPo−1 plays an important role in alleviating CCR.Furthermore,we replaced the C-terminus of Cre1 with that of CreAPo−1 in T.reesei(Tr-0)and generated Tr-1.As a control,the C-terminus of Cre1 was truncated and Tr-2 was generated.The transcriptional profiles of these transformants revealed that the C-terminal chimera greatly improves cellulase transcription in the presence of glucose and thus upregulates cellulase in the presence of glucose and weakens CCR,consistent with truncating the C-terminus of Cre1 in Tr-0.Therefore,we propose constructing a C-terminal chimera as a new strategy to improve cellulase production and alleviate CCR in the presence of glucose.

FINANCIAL REPRESSION, FINANCIAL LEGAL GOVERNANCE AND ECONOMIC GROWTH IN CHINA

Financial repression usually exists in developing countries. By nature, it as like a hidden tax and can liquidate public debt of the government effectively. The policy of financial repression will likely hinder financial deepening, negatively influence the building-up of efficient and inclusive financial systems, and eventually harm sustainable economic growth in the long run. The fine legal infrastructure plays an important role in financial deepening and development. In China the major measures to reduce financial repression and improve the legal governance in finance are the following： the strict respect and protection of private property rights, including the obligation rights of the common depositors against the banks and the shareholders＇ rights of the common investors, the respect and protection of the contract freedom and contract enforcement, the sequential openness of financial market entry and introduction of the principle of free and equal competition in the financial market, and the improvement of the judicial system to increase the adaptability of Chinese law, such as the strengthening of judicial independence and the establishment of case law.

Brassinosteroids inhibit miRNA-mediated translational repression by decreasing AGO1 on the endoplasmic reticulum

Translational repression is a conserved mechanism in microRNA(miRNA)-guided gene silencing.In Arabidopsis,ARGONAUTE1(AGO1),the major miRNA effector,localizes in the cytoplasm for mRNA cleavage and at the endoplasmic reticulum(ER)for translational repression of target genes.However,the mechanism underlying miRNA-mediated translational repression is poorly understood.In particular,how the subcellular partitioning of AGO1 is regulated is largely unexplored.Here,we show that the plant hormone brassinosteroids(BRs)inhibit miRNA-mediated translational repression by negatively regulating the distribution of AGO1 at the ER in Arabidopsis thaliana.We show that the protein levels rather than the transcript levels of miRNA target genes were reduced in BR-deficient mutants but increased under BR treatments.The localization of AGO1 at the ER was significantly decreased under BR treatments while it was increased in the BR-deficient mutants.Moreover,ROTUNDIFOLIA3(ROT3),an enzyme involved in BR biosynthesis,co-localizes with AGO1 at the ER and interacts with AGO1 in a GW motif-dependent manner.Complementation analysis showed that the AGO1-ROT3 interaction is necessary for the function of ROT3.Our findings provide new clues to understand how miRNA-mediated gene silencing is regulated by plant endogenous hormones.

Distinct gene expression pattern of RUNX1 mutations coordinated by target repression and promoter hypermethylation in acute myeloid leukemia

Runt-related transcription factor 1(RUNX1)is an essential regulator of normal hematopoiesis.Its dysfunction,caused by either fusions or mutations,is frequently reported in acute myeloid leukemia(AML).However,RUNX1 mutations have been largely under-explored compared with RUNX1 fusions mainly due to their elusive genetic characteristics.Here,based on 1741 patients with AML,we report a unique expression pattern associated with RUNX1 mutations in AML.This expression pattern was coordinated by target repression and promoter hypermethylation.We first reanalyzed a joint AML cohort that consisted of three public cohorts and found that RUNX1 mutations were mainly distributed in the Runt domain and almost mutually exclusive with NPM1 mutations.Then,based on RNA-seq data from The Cancer Genome Atlas AML cohort,we developed a 300-gene signature that significantly distinguished the patients with RUNX1 mutations from those with other AML subtypes.Furthermore,we explored the mechanisms underlying this signature from the transcriptional and epigenetic levels.Using chromatin immunoprecipitation sequencing data,we found that RUNX1 target genes tended to be repressed in patients with RUNX1 mutations.Through the integration of DNA methylation array data,we illustrated that hypermethylation on the promoter regions of RUNX1-regulated genes also contributed to dysregulation in RUNX1-mutated AML.This study revealed the distinct gene expression pattern of RUNX1 mutations and the underlying mechanisms in AML development.

Hot Money Flows,Commodity Price Cycles and Financial Repression in the USA and China:The Consequences of Near-zero US Interest Rates

Under near-zero US interest rates, the international dollar standard malfunctions. Emerging markets with naturally higher interest rates are swamped with hot money inflows. Emerging market central banks intervene to prevent their currencies from rising precipitately. They lose monetary control and domestic prices begin inflating. Primary commodity prices rise worldwide unless interrupted by an international banking crisis＇. This cyclical inflation on the dollar＇s periphery only registers in the US core eonsumer price index with a long lag. The zero interest rate policy also fails to stimulate the US economy as domestic finaneial intermediation by banks and money market mutual funds is repressed. Because China is forced to keep its interest rates below market-clearing levels, it also suffers from finaneial repression, although in a form differing from that in the USA.

Characteristics of and Risk Factors Associated with Self-Reported Sexual Repression among Internal Migrants in China: A Large-Scale Cross-Sectional Study

Objective:This large-scale cross-sectional study aims to identify the characteristics of and risk factors associated with sexual repression among internal migrants in China.Methods:Between August 2013 and August 2015,a total of 8,669 internal migrants from four major cities in China(Beijing,Shanghai,Chengdu,and Chongqing)voluntarily participated in our study.They were interviewed,and the data on their demographic information,occupation,and sexual activities were collected.The Chi-square test and multiple logistic regressions were conducted to identify significant associations.A stepwise method was adopted for the selection of variables.Results:There were 3,597(41.49%)males and 5,072(58.51%)females in total.A higher percentage of males reported that they felt sexual repression compared to females(14.43%vs.9.21%).After adjusting for other covariates,the consequence was showed that male migrants working for more than 5 days were more likely to report sexual repression(odds ratio[OR]=1.40,P<0.05).Living in a collective dormitory with others was also a risk factor for male migrants.The longer males spent with their partners,the less sexual repression occurred(OR=0.94,P<0.05).Similarly,agricultural household registration status and working for more than 5 days increased the risk for sexual repression among female migrants(OR=1.41 and OR=1.46,respectively,P<0.05).Frequent and constructive communication also protected females against sexual repression(P<0.05).Well-educated females experienced relatively less sexual repression when compared to their counterparts with less education(P<0.05).Conclusions:Sexual repression was significantly associated with a few demographic,occupational,and sexual risk factors.Meaningful differences have been identified between male and female migrants.More effective intervention programs such as safeguard measures and welfare policies should be designed and implemented for a majority of female migrants and for those with agricultural household registration status.