scholarly journals Fine chromatin-driven mechanism of transcription interference by antisense noncoding transcription

2019 ◽  
Author(s):  
Jatinder Kaur Gill ◽  
Andrea Maffioletti ◽  
Varinia García-Molinero ◽  
Françoise Stutz ◽  
Julien Soudet
Keyword(s):  
Rna Polymerase Ii ◽  
Nucleosome Occupancy ◽  
List Type ◽  
Gene Promoters ◽  
Chromatin Remodeler ◽  
The Relationship ◽  
Eukaryotic Genomes ◽  
Transcription Interference ◽  
Interference Mechanism ◽  
Noncoding Transcription

AbstractEukaryotic genomes are almost entirely transcribed by RNA polymerase II (RNAPII). Consequently, the transcription of long noncoding RNAs (lncRNAs) often overlaps with coding gene promoters triggering potential gene repression through a poorly characterized mechanism of transcription interference. In this study, we propose a global model of chromatin-based transcription interference in Saccharomyces cerevisiae (S. cerevisiae). By using a noncoding transcription inducible strain, we analyzed the relationship between antisense elongation and coding sense repression, nucleosome occupancy and transcription-associated histone modifications using near-base pair resolution techniques. We show that antisense noncoding transcription leads to the deaceylation of a subpopulation of −1/+1 nucleosomes associated with increased H3K36 trimethylation (H3K36me3). Reduced acetylation results in decreased binding of the RSC chromatin remodeler at −1/+1 nucleosomes and subsequent sliding into the Nucleosome-Depleted Region (NDR) hindering Pre-Initiation Complex (PIC) association. Finally, we extend our model by showing that natural antisense noncoding transcription significantly represses around 20% of S. cerevisiae genes through this chromatin-based transcription interference mechanism.HighlightsInduction of antisense noncoding transcription leads to −1/+1 nucleosome sliding that competes with sense transcription PIC deposition.Antisense induction leads to a subpopulation of H3K36me3 nucleosomes differently positioned compared to H3K18ac nucleosomes.RSC chromatin remodeler recruitment to −1/+1 nucleosomes is modulated by histone acetylation levels.20% of S. cerevisiae genes are significantly repressed by this antisense-dependent chromatin-based transcription interference mechanism.

scholarly journals RSC-mediated nucleosome positioning and GRFs form barriers in promoters to limit divergent noncoding transcription

2021 ◽  
Author(s):  
Andrew Wu ◽  
Claudia Vivori ◽  
Harshil Patel ◽  
Theodora Sideri ◽  
Folkert van Werven
Keyword(s):  
Transcription Initiation ◽  
Nucleosome Occupancy ◽  
Nucleosome Positioning ◽  
Gene Promoters ◽  
Protein Coding ◽  
Transcription Start Sites ◽  
Binding Factor ◽  
Cryptic Transcription ◽  
Divergent Transcription ◽  
Noncoding Transcription

The directionality of gene promoters - the ratio of protein-coding over divergent noncoding transcription - is highly variable and regulated. How promoter directionality is controlled remains poorly understood. We show that the chromatin remodelling complex RSC and general regulatory factors (GRFs) dictate promoter directionality by attenuating divergent transcription. Depletion of RSC increased divergent noncoding transcription and decreased protein-coding transcription at promoters with strong directionality. Consistent with RSCs role in regulating chromatin, RSC depletion impacts nucleosome occupancy upstream of the nucleosome depleted region where divergent transcription initiates, suggesting that nucleosome positioning at the 5 prime border of gene promoters physically blocks the recruitment of the transcription machinery and inhibits initiation of divergent transcription. Highly directional promoters were also enriched for the binding of GRFs such as Reb1 and Abf1. Furthermore, ectopic targeting of divergent transcription initiation sites with GRFs or the dCas9 protein can suppress divergent transcription. Our data suggest that RSC-mediated nucleosome positioning and GRFs play a pervasive role in repressing divergent transcription. We propose that any DNA binding factor, when stably associated with cryptic transcription start sites, can form a barrier for repressing divergent transcription. Our study provides an explanation as to why certain promoters are more directional than others.

scholarly journals Antisense-mediated repression of SAGA-dependent genes involves the HIR histone chaperone

2021 ◽  
Author(s):  
Julien Soudet ◽  
Nissrine Beyrouthy ◽  
Anna Marta Pastucha ◽  
Andrea Maffioletti ◽  
Zahra Bakir ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Transcription Initiation ◽  
De Novo ◽  
Antisense Transcription ◽  
Histone Chaperone ◽  
Gene Promoters ◽  
Genome Wide ◽  
Chaperone Complex ◽  
Histone Deposition ◽  
Transcription Interference

Eukaryotic genomes are pervasively transcribed by RNA polymerase II (RNAPII), and transcription of long non-coding RNAs often overlaps with coding gene promoters. This might lead to coding gene repression in a process named Transcription Interference (TI). In Saccharomyces cerevisiae (S. cerevisiae), TI is mainly driven by antisense non-coding transcription and occurs through re-shaping of promoter Nucleosome-Depleted Regions (NDRs). In this study, we developed a genetic screen to identify new players involved in Antisense-Mediated Transcription Interference (AMTI). Among the candidates, we found the HIR histone chaperone complex known to be involved in de novo histone deposition. Using genome-wide approaches, we reveal that HIR-dependent histone deposition represses the promoters of SAGA-dependent genes via antisense non-coding transcription. However, while antisense transcription is enriched at promoters of SAGA-dependent genes, this feature is not sufficient to define the mode of gene regulation. We further show that the balance between HIR-dependent nucleosome incorporation and transcription factor binding at promoters directs transcription into a SAGA- or TFIID-dependent regulation. This study sheds light on a new connection between antisense non-coding transcription and the nature of coding transcription initiation.

scholarly journals Dynamic Nature of Cleavage Bodies and Their Spatial Relationship to DDX1 Bodies, Cajal Bodies, and Gems

2006 ◽  
Vol 17 (3) ◽  
pp. 1126-1140 ◽  
Author(s):  
Lei Li ◽  
Ken Roy ◽  
Sachin Katyal ◽  
Xuejun Sun ◽  
Stacey Bléoo ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Actin Polymerization ◽  
Spatial Relationship ◽  
S Phase ◽  
Nuclear Bodies ◽  
Cajal Bodies ◽  
Rna Transcription ◽  
Nuclear Structures ◽  
The Relationship ◽  
Striking Effect

DDX1 bodies, cleavage bodies, Cajal bodies (CBs), and gems are nuclear suborganelles that contain factors involved in RNA transcription and/or processing. Although all four nuclear bodies can exist as distinct entities, they often colocalize or overlap with each other. To better understand the relationship between these four nuclear bodies, we examined their spatial distribution as a function of the cell cycle. Here, we report that whereas DDX1 bodies, CBs and gems are present throughout interphase, CPSF-100-containing cleavage bodies are predominantly found during S and G2 phases, whereas CstF-64-containing cleavage bodies are primarily observed during S phase. All four nuclear bodies associate with each other during S phase, with cleavage bodies colocalizing with DDX1 bodies, and cleavage bodies/DDX1 bodies residing adjacent to gems and CBs. Although inhibitors of RNA transcription had no effect on DDX1 bodies or cleavage bodies, inhibitors of DNA replication resulted in loss of CstF-64-containing cleavage bodies. A striking effect on nuclear structures was observed with latrunculin B, an inhibitor of actin polymerization, resulting in the formation of needlelike nuclear spicules made up of CstF-64, CPSF-100, RNA, and RNA polymerase II. Our results suggest that cleavage body components are highly dynamic in nature.

scholarly journals Metabolic syndrome in psychiatry: advances in understanding and management

2014 ◽  
Vol 20 (2) ◽  
pp. 101-112 ◽  
Author(s):  
Cyrus S. H. Ho ◽  
Melvyn W. B. Zhang ◽  
Anselm Mak ◽  
Roger C. M. Ho
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Psychiatric Disorders ◽  
Psychiatric Patients ◽  
Learning Objectives ◽  
List Type ◽  
Type Number ◽  
Unhealthy Lifestyle ◽  
Definition Of ◽  
The Relationship

SummaryMetabolic syndrome comprises a number of cardiovascular risk factors that increase morbidity and mortality. The increase in incidence of the syndrome among psychiatric patients has been unanimously demonstrated in recent studies and it has become one of the greatest challenges in psychiatric practice. Besides the use of psychotropic drugs, factors such as genetic polymorphisms, inflammation, endocrinopathies and unhealthy lifestyle contribute to the association between metabolic syndrome and a number of psychiatric disorders. In this article, we review the current diagnostic criteria for metabolic syndrome and propose clinically useful guidelines for psychiatrists to identify and monitor patients who may have the syndrome. We also outline the relationship between metabolic syndrome and individual psychiatric disorders, and discuss advances in pharmacological treatment for the syndrome, such as metformin.LEARNING OBJECTIVES•Be familiar with the definition of metabolic syndrome and its parameters of measurement.•Appreciate how individual psychiatric disorders contribute to metabolic syndrome and vice versa.•Develop a framework for the prevention, screening and management of metabolic syndrome in psychiatric patients.

Effect of Vibration on Rapeseed Header Loss and Optimization of Header Frame

2021 ◽  
Vol 64 (4) ◽  
pp. 1247-1258
Author(s):  
Yang Li ◽  
Lizhang Xu ◽  
Zhipeng Gao ◽  
En Lu ◽  
Yaoming Li
Keyword(s):  
Modal Analysis ◽  
Engine Speed ◽  
Vibration Measurement ◽  
List Type ◽  
Positive Correlation ◽  
Combine Harvester ◽  
Analysis System ◽  
Combine Harvesters ◽  
Relationship Of ◽  
The Relationship

HighlightsThe relationship of vibration and header loss was studied by multi-point vibration measurement and loss collection test.There was an approximately linear positive correlation between total header vibration and total rapeseed header loss.The header frame was analyzed and optimized through modal simulation and testing.The total rapeseed header loss of the improved header was reduced by 33.2% to 46.9%.Abstract. In view of the current large rapeseed header losses of rape combine harvesters, the effects of the header on rapeseed header loss were studied from the perspective of vibration. First, the vibrations at various measuring points on the header during rape harvest were studied using a data acquisition and analysis system while performing collection tests of rapeseed header loss with the sample slot method. The relationships between total header vibration and total rapeseed header loss and between vertical cutter vibration and rapeseed vertical cutter loss were shown to have a positive correlation, and they all increased with the increase in engine speed. Vertical cutter loss accounted for 31.2% to 42.4% of the total rapeseed header loss. Modal analysis and optimization of the header frame were then performed by simulation and test. The natural frequencies of the first-order and second-order modes of the optimized header were increased, and the possibility of resonance with other working parts was eliminated. Finally, the improved header was tested during rape harvest. The results showed that the total vibration of the improved header was reduced by 19.9% to 43.9%, and the total rapeseed header loss was reduced by 33.2% to 46.9%. The vertical cutter vibration was reduced by 30.5% to 49.8%, and the rapeseed vertical cutter loss was reduced by 20.8% to 34.7%. In addition, the vibration and rapeseed loss of the improved header had relatively slow rates of increase with the increase in engine speed. The method of reducing rapeseed loss by reducing the header vibration achieved an obvious and positive effect. Keywords: Frame optimization, Modal analysis, Rape combine harvester, Rapeseed header loss, Vibration.

Depression impact on the sexual desire

2011 ◽  
Vol 26 (S2) ◽  
pp. 1549-1549
Author(s):  
M. Lourenço ◽  
L.P. Azevedo ◽  
J.L. Gouveia
Keyword(s):  
Sexual Desire ◽  
Depressive Symptomatology ◽  
Psychiatric Patients ◽  
Severe Depression ◽  
List Type ◽  
Sexual Performance ◽  
Average Value ◽  
Treatment Of Depression ◽  
The One ◽  
The Relationship

IntroductionDepression as a pathology and the side effects of pharmacology therapy have been pointed proven to be as responsible for the lack of sexual desire. Among the drugs used in the treatment of depression, anti-depressives are the ones mostly connected to sexual dysfunction.Aims /objectivesTo study the relationship between depression and its impact on the sexual desire in psychiatric patients.MethodsThe chosen sample is composed of 89 subjects, 73 females and 16 males, with ages ranging from 21 to 70 years, who present with depressive symptomatology (mild to moderate symptomatology (MMS) and severe symptomatology (SS).To each patient 3 instruments were applied: 1)Questionnaire used to collect demographic and clinical data from the sample;2)Instrument of estimation of the depression degree (BDI - Beck Depression Inventory);3)Instrument of valuation of the sexual desire (SDS - Sexual Desire Scale).ResultsDepression average value obtained with BDI was 25.58 (SD = 11.86). The majority was satisfied with their marital relationship (72.7% and 52.9%, respectively), and the group with most sexual damaged (actual sexual performance regarding sexual desire) being the one with severe depression (54.5% versus 82.4%, respectively). Regarding total SDS value, the group with MMD present with higher levels of sexual desire (M = 54.93; DP = 14.56) than the group with SD (M = 41.82; DP = 11.86).ConclusionsThis study presents an exploratory character and the obtained results revealed that depressive symptomatology severity is directly related with sexual desire, by saying the higher the depression's severity is the lower sexual desire will be.

scholarly journals The chromatin remodeler Ino80 mediates RNAPII pausing site determination

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Youngseo Cheon ◽  
Sungwook Han ◽  
Taemook Kim ◽  
Daehee Hwang ◽  
Daeyoup Lee
Keyword(s):  
Rna Polymerase Ii ◽  
Transcriptional Start Site ◽  
Regulation Of Gene Expression ◽  
Embryonic Stem ◽  
Start Site ◽  
Chromatin Remodeler ◽  
Close Relationship ◽  
Early Transcription ◽  
Different Characteristics

Abstract Background Promoter-proximal pausing of RNA polymerase II (RNAPII) is a critical step for the precise regulation of gene expression. Despite the apparent close relationship between promoter-proximal pausing and nucleosome, the role of chromatin remodeler governing this step has mainly remained elusive. Results Here, we report highly confined RNAPII enrichments downstream of the transcriptional start site in Saccharomyces cerevisiae using PRO-seq experiments. This non-uniform distribution of RNAPII exhibits both similar and different characteristics with promoter-proximal pausing in Schizosaccharomyces pombe and metazoans. Interestingly, we find that Ino80p knockdown causes a significant upstream transition of promoter-proximal RNAPII for a subset of genes, relocating RNAPII from the main pausing site to the alternative pausing site. The proper positioning of RNAPII is largely dependent on nucleosome context. We reveal that the alternative pausing site is closely associated with the + 1 nucleosome, and nucleosome architecture around the main pausing site of these genes is highly phased. In addition, Ino80p knockdown results in an increase in fuzziness and a decrease in stability of the + 1 nucleosome. Furthermore, the loss of INO80 also leads to the shift of promoter-proximal RNAPII toward the alternative pausing site in mouse embryonic stem cells. Conclusions Based on our collective results, we hypothesize that the highly conserved chromatin remodeler Ino80p is essential in establishing intact RNAPII pausing during early transcription elongation in various organisms, from budding yeast to mouse.

scholarly journals HSFs drive stress type-specific transcription of genes and enhancers

2021 ◽  
Author(s):  
Samu V Himanen ◽  
Mikael C Puustinen ◽  
Alejandro J Da Silva ◽  
Anniina Vihervaara ◽  
Lea Sistonen
Keyword(s):  
Oxidative Stress ◽  
Heat Shock ◽  
Rna Polymerase Ii ◽  
Molecular Mechanisms ◽  
Gene Promoters ◽  
Heat Shock Factors ◽  
Pol Ii ◽  
Bona Fide ◽  
Stressed Cells ◽  
First Time

Reprogramming of transcription is critical for the survival under cellular stress. Heat shock has provided an excellent model to investigate nascent transcription in stressed cells, but the molecular mechanisms orchestrating RNA synthesis during other types of stress are unknown. We utilized PRO-seq and ChIP-seq to study how Heat Shock Factors, HSF1 and HSF2, coordinate transcription at genes and enhancers upon oxidative stress and heat shock. We show that pause-release of RNA polymerase II (Pol II) is a universal mechanism regulating gene transcription in stressed cells, while enhancers are activated at the level of Pol II recruitment. Moreover, besides functioning as conventional promoter-binding transcription factors, HSF1 and HSF2 bind to stress-induced enhancers to trigger Pol II pause-release from poised gene promoters. Importantly, HSFs act at distinct genes and enhancers in a stress type-specific manner. HSF1 binds to many chaperone genes upon oxidative and heat stress but activates them only in heat-shocked cells. Under oxidative stress, HSF1 and HSF2 trans-activate genes independently of each other, demonstrating, for the first time, that HSF2 is a bona fide transcription factor. Taken together, we show that HSFs function as multi-stress-responsive factors that activate specific genes and enhancers when encountering changes in temperature and redox state.

scholarly journals Influenza Virus and Chromatin: Role of the CHD1 Chromatin Remodeler in the Virus Life Cycle

2016 ◽  
Vol 90 (7) ◽  
pp. 3694-3707 ◽  
Author(s):  
Laura Marcos-Villar ◽  
Alejandra Pazo ◽  
Amelia Nieto
Keyword(s):  
Influenza Virus ◽  
Rna Polymerase Ii ◽  
Polymerase Activity ◽  
Virus Multiplication ◽  
Viral Transcription ◽  
Chromatin Remodeler ◽  
Viral Polymerase ◽  
Chromatin Dynamics ◽  
Rnap Ii ◽  
Cellular Transcription

ABSTRACTInfluenza A virus requires ongoing cellular transcription to carry out the cap-snatching process. Chromatin remodelers modify chromatin structure to produce an active or inactive conformation, which enables or prevents the recruitment of transcriptional complexes to specific genes; viral transcription thus depends on chromatin dynamics. Influenza virus polymerase associates with chromatin components of the infected cell, such as RNA polymerase II (RNAP II) or the CHD6 chromatin remodeler. Here we show that another CHD family member, CHD1 protein, also interacts with the influenza virus polymerase complex. CHD1 recognizes the H3K4me3 (histone 3 with a trimethyl group in lysine 4) histone modification, a hallmark of active chromatin. Downregulation of CHD1 causes a reduction in viral polymerase activity, viral RNA transcription, and the production of infectious particles. Despite the dependence of influenza virus on cellular transcription, RNAP II is degraded when viral transcription is complete, and recombinant viruses unable to degrade RNAP II show decreased pathogenicity in the murine model. We describe the CHD1–RNAP II association, as well as the parallel degradation of both proteins during infection with viruses showing full or reduced induction of degradation. The H3K4me3 histone mark also decreased during influenza virus infection, whereas a histone mark of inactive chromatin, H3K27me3, remained unchanged. Our results indicate that CHD1 is a positive regulator of influenza virus multiplication and suggest a role for chromatin remodeling in the control of the influenza virus life cycle.IMPORTANCEAlthough influenza virus is not integrated into the genome of the infected cell, it needs continuous cellular transcription to synthesize viral mRNA. This mechanism implies functional association with host genome expression and thus depends on chromatin dynamics. Influenza virus polymerase associates with transcription-related factors, such as RNA polymerase II, and with chromatin remodelers, such as CHD6. We identified the association of viral polymerase with another chromatin remodeler, the CHD1 protein, which positively modulated viral polymerase activity, viral RNA transcription, and virus multiplication. Once viral transcription is complete, RNAP II is degraded in infected cells, probably as a virus-induced mechanism to reduce the antiviral response. CHD1 associated with RNAP II and paralleled its degradation during infection with viruses that induce full or reduced degradation. These findings suggest that RNAP II degradation and CHD1 degradation cooperate to reduce the antiviral response.

scholarly journals Regulation of alternative polyadenylation in the yeast Saccharomyces cerevisiae by histone H3K4 and H3K36 methyltransferases

2020 ◽  
Vol 48 (10) ◽  
pp. 5407-5425 ◽  
Author(s):  
Katarzyna Kaczmarek Michaels ◽  
Salwa Mohd Mostafa ◽  
Julia Ruiz Capella ◽  
Claire L Moore
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Rna Polymerase Ii ◽  
Nucleosome Occupancy ◽  
Alternative Polyadenylation ◽  
Nutritional Stress ◽  
Yeast Saccharomyces Cerevisiae ◽  
Terminal Domain ◽  
Histone H3k4 ◽  
Rnap Ii ◽  
And Control

Abstract Adjusting DNA structure via epigenetic modifications, and altering polyadenylation (pA) sites at which precursor mRNA is cleaved and polyadenylated, allows cells to quickly respond to environmental stress. Since polyadenylation occurs co-transcriptionally, and specific patterns of nucleosome positioning and chromatin modifications correlate with pA site usage, epigenetic factors potentially affect alternative polyadenylation (APA). We report that the histone H3K4 methyltransferase Set1, and the histone H3K36 methyltransferase Set2, control choice of pA site in Saccharomyces cerevisiae, a powerful model for studying evolutionarily conserved eukaryotic processes. Deletion of SET1 or SET2 causes an increase in serine-2 phosphorylation within the C-terminal domain of RNA polymerase II (RNAP II) and in the recruitment of the cleavage/polyadenylation complex, both of which could cause the observed switch in pA site usage. Chemical inhibition of TOR signaling, which causes nutritional stress, results in Set1- and Set2-dependent APA. In addition, Set1 and Set2 decrease efficiency of using single pA sites, and control nucleosome occupancy around pA sites. Overall, our study suggests that the methyltransferases Set1 and Set2 regulate APA induced by nutritional stress, affect the RNAP II C-terminal domain phosphorylation at Ser2, and control recruitment of the 3′ end processing machinery to the vicinity of pA sites.

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