scholarly journals SWI/SNF coordinates transcriptional activation through Rpd3-mediated histone hypoacetylation during quiescence entry

2018 ◽  
Author(s):  
Marla M. Spain ◽  
Keean C.A. Braceros ◽  
Toshio Tsukiyama ◽  

SummaryWhether or not a cell chooses to divide is a tightly regulated and extremely important decision. Cells from yeast to human are able to reversibly exit the cell cycle in response to environmental changes such as nutritional changes or removal of growth cues to become quiescent. An inappropriate response to environmental cues can result in overproliferation which can lead to cancer, or a failure to proliferate which can result in developmental defects, premature aging and defects in wound healing. While many of the cell signaling pathways involved in regulating cellular quiescence have been identified, how these pathways translate their messages into transcriptional outputs is not well characterized. We previously showed that the histone deacetylase Rpd3 mediates global histone deacetylation and transcription repression upon quiescence entry. How the activation of quiescence-specific genes occurs in the midst of this transcriptionally repressive environment is not well understood. We show that the SWI/SNF chromatin remodeling complex activates quiescence specific genes to promote entry into quiescence. We additionally show that SWI/SNF binding early during quiescence entry is important for facilitating localization of the transcriptional activator Gis1, as well as histone H4 hypoacetylation in coding regions later on. The increase in H4 acetylation that we observe at Snf2-regulated genes upon Snf2 depletion corresponds to a decrease in promoter-bound Rpd3, suggesting that Snf2 remodels chromatin not only to facilitate activator binding, but also the binding of Rpd3. These observations provide mechanistic insight as to how quiescence-specific genes can be activated in the face of global deacetylation and transcription repression.


Genetics ◽  
2000 ◽  
Vol 154 (4) ◽  
pp. 1561-1576
Author(s):  
Neil Macpherson ◽  
Vivien Measday ◽  
Lynda Moore ◽  
Brenda Andrews

Abstract In Saccharomyces cerevisiae, the Swi6 protein is a component of two transcription factors, SBF and MBF, that promote expression of a large group of genes in the late G1 phase of the cell cycle. Although SBF is required for cell viability, SWI6 is not an essential gene. We performed a synthetic lethal screen to identify genes required for viability in the absence of SWI6 and identified 10 complementation groups of swi6-dependent lethal mutants, designated SLM1 through SLM10. We were most interested in mutants showing a cell cycle arrest phenotype; both slm7-1 swi6Δ and slm8-1 swi6Δ double mutants accumulated as large, unbudded cells with increased 1N DNA content and showed a temperature-sensitive growth arrest in the presence of Swi6. Analysis of the transcript levels of cell cycle-regulated genes in slm7-1 SWI6 mutant strains at the permissive temperature revealed defects in regulation of a subset of cyclin-encoding genes. Complementation and allelism tests showed that SLM7 is allelic with the TAF17 gene, which encodes a histone-like component of the general transcription factor TFIID and the SAGA histone acetyltransferase complex. Sequencing showed that the slm7-1 allele of TAF17 is predicted to encode a version of Taf17 that is truncated within a highly conserved region. The cell cycle and transcriptional defects caused by taf17slm7-1 are consistent with the role of TAFIIs as modulators of transcriptional activation and may reflect a role for TAF17 in regulating activation by SBF and MBF.



2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Daniel Wittmann ◽  
Neha Sinha ◽  
Bernhard Grimm

AbstractPlastids are specialized organelles found in plants, which are endowed with their own genomes, and differ in many respects from the intracellular compartments of organisms belonging to other kingdoms of life. They differentiate into diverse, plant organ-specific variants, and are perhaps the most versatile organelles known. Chloroplasts are the green plastids in the leaves and stems of plants, whose primary function is photosynthesis. In response to environmental changes, chloroplasts use several mechanisms to coordinate their photosynthetic activities with nuclear gene expression and other metabolic pathways. Here, we focus on a redox-based regulatory network composed of thioredoxins (TRX) and TRX-like proteins. Among multiple redox-controlled metabolic activities in chloroplasts, tetrapyrrole biosynthesis is particularly rich in TRX-dependent enzymes. This review summarizes the effects of plastid-localized reductants on several enzymes of this pathway, which have been shown to undergo dithiol-disulfide transitions. We describe the impact of TRX-dependent control on the activity, stability and interactions of these enzymes, and assess its contribution to the provision of adequate supplies of metabolic intermediates in the face of diurnal and more rapid and transient changes in light levels and other environmental factors.



2016 ◽  
Vol 34 (1) ◽  
pp. 1-44
Author(s):  
Jeffrey S. Adler

On May 11, 1938, two New Orleans policemen entered the Astoria Restaurant, marched to the kitchen, and approached Loyd D. T. Washington, a 41-year-old African American cook. They informed Washington that they would be taking him to the First Precinct station for questioning, although they assured the cook that he need not change his clothes and “should be right back” to the “Negro restaurant,” where he had worked for 3 years. Immediately after arriving at the station house, police officers “surrounded” Washington, showed him a photograph of a man, and announced that he had killed a white man in Yazoo City, Mississippi, 20 years earlier. When Washington insisted that he did not know the man in the photograph, that he had never been to (or even heard of) Yazoo City, and that he had been in the army at the time of the murder, the law enforcers confined him in a cell, although they had no warrant for his arrest and did not charge him with any crime. The following day, a detective brought him to the “show-up room” in the precinct house, where he continued the interrogation and, according to Washington, “tried to make me sign papers stating that I had killed a white man” in Mississippi. As every African American New Orleanian knew, the show-up (or line-up) room was the setting where detectives tortured suspects and extracted confessions. “You know you killed him, Nigger,” the detective roared. Washington, however, refused to confess, and the detective began punching him in the face, knocking out five of his teeth. After Washington crumbled to the floor, the detective repeatedly kicked him and broke one of his ribs. The beating continued for an hour, until other policemen restrained the detective, saying “give him a chance to confess and if he doesn't you may start again.” But Washington did not confess, and the violent interrogation began anew. A short time later, another police officer interrupted the detective, telling him “do not kill this man in here, after all he is wanted in Yazoo City.” Bloodied and writhing in pain, Washington asked to contact his family, but the request was ignored. Because he had not been formally charged with a crime, New Orleans law enforcers believed that Washington had no constitutional protection again self-incrimination or coercive interrogation and no right to an arraignment or bail, and they had no obligation to contact his relatives or to provide medical care for him.



2007 ◽  
Vol 66 (3) ◽  
pp. 713-726 ◽  
Author(s):  
Ludmila V. Roze ◽  
Anna E. Arthur ◽  
Sung-Yong Hong ◽  
Anindya Chanda ◽  
John E. Linz


1993 ◽  
Vol 120 (2) ◽  
pp. 277-290 ◽  
Author(s):  
J Sommerville ◽  
J Baird ◽  
B M Turner

Lampbrush chromosomes from oocytes of the amphibian Triturus cristatus have been used to examine the role of histone acetylation in transcription by indirect immunofluorescence with antisera to H4 acetylated at specific lysine residues. Electrophoresis on acid-urea-Triton gels and Western blotting have confirmed the specificity of these antisera and defined the order in which particular lysine residues are acetylated in amphibian cells. As in mammals, lysine 16 is acetylated first, followed by 8 and/or 12 and then 5. With lampbrush chromosomes from immature (previtellogenic) oocytes, antisera to H4 acetylated at lysines 8, 12, and 16 labeled fluorescent foci at the bases of transcription loops. Antisera to H4 acetylated at lysine 5 labeled weakly (i.e., the tri- and tetraacetylated isoforms must be rare). Loops showed weak labeling of the chromatin axis but intense fluorescence at particular points, which probably represent incompletely decondensed chromatin. The RNP matrix of loops, including the RNP-rich sphere bodies and the dense matrix of "marker" loops, was not labeled. Treatment of immature oocytes with butyrate for 12 h to inhibit histone deacetylation did not affect immunolabeling, suggesting that turnover of H4 acetates is slow. In contrast, in chromosomes from mature oocytes, in which loops have retracted and transcription is low, butyrate caused an increase in labeling with all antisera, followed by the appearance of vestigial loops, weakly labeled, but with regions of intense fluorescence. These loops contain RNP and are presumably transcriptionally active. We conclude that H4 acetates turn over more rapidly in mature than immature oocytes and that histone hyperacetylation precedes, and possibly induces, loop formation and transcriptional activation.



2018 ◽  
Vol 20 (11) ◽  
pp. 1034-1045 ◽  
Author(s):  
Sagi Denenberg ◽  
Maya Bräm Dubé

Practical relevance: When a cat is presented for evaluation of a problem behaviour, it is likely that the cat’s wellbeing is negatively affected by the condition. In addition, the owners and any other animals around the cat may also be experiencing negative consequences. When managing these cases, it is important to consider all options (including behaviour modification, environmental changes, medications) that can help to reach an optimal solution. Medication cannot teach the cat how to behave or change a particular behaviour; it can, however, reduce arousal, excitability, reactivity and anxiety. Rationale: The rationale for using psychoactive medications in behavioural medicine, or veterinary psychiatry, is to increase the wellbeing of the animal and to aid the owner and practitioner in managing problem behaviours. Medications should always be used as an adjunct to behavioural and environmental modification. Clinical challenges: Many psychoactive medications cannot be used in the face of certain physical illnesses or concurrently with other medications. Some medications may also have side effects, not be effective at the recommended dose or have a paradoxical effect. Furthermore, success is reliant on the owner being able to administer the medication. Aims: This article aims to guide practitioners by discussing questions such as how to choose the appropriate medication, how to dose it and how long to use it. The psychoactive medications most commonly used in feline medicine are reviewed, as well as some that are newer or less common. Evidence base: Data for the use of medications in cats is limited, with just a small number of clinical-, species- and problem-directed studies available, and a few more case series and case reports. Where feline-specific research is not available, the authors have drawn upon research published in other species, such as humans, dogs and rats, as well as anecdotal reports and expert opinions.



1968 ◽  
Vol 16 (4) ◽  
pp. 264-274
Author(s):  
D.T. Edwards

Two very different cases of small-scale farm development in the Commonwealth Caribbean are reviewed. One is Jamaican small farming, which responded little to considerable efforts made for its improvement by the Government agencies. The other is market gardening at Aranjuez, Trinidad where production grew at an extremely rapid rate in the face of intense and antagonistic competition between the market gardeners and without significant direct assistance by official agencies. The conclusions include a number of possible strategies for farm development, comprising individual or collective persuasion, coercion, creation of new farms, and environmental changes. T. A. (Abstract retrieved from CAB Abstracts by CABI’s permission)



2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Yoichi Sunagawa ◽  
Yasufumi Katanasaka ◽  
Taishi Terada ◽  
Yuichi Watanabe ◽  
Hiromichi Wada ◽  
...  

Background: A zinc finger protein GATA4 is one of hypertrophy-responsive transcription factors, and increases its DNA-binding and transcriptional activities in response to hypertrophic stimuli in cardiomyocytes. Activation of GATA4 during this process is mediated, in part, through acetylation by intrinsic histone acetyltransferases such as a transcriptional coactivator p300. Here, we show that retinoblastoma protein (Rb)-associated protein 48 and 46 (RbAp48, RbAp46), components of NuRD (nucleosome remodeling and deacetylase) complex that has been implicated in chromatin remodeling and transcriptional repression associated with histone deacetylation, are novel components of p300/GATA4 complex. However, the precise functional relationships among p300, GATA4, RbAp48, and RbAp46 remain unknown. Methods and Results: A series of GST pull-down assays revealed that the C-terminal domain of RbAp48/46 bound to the N-terminal transcriptional activation domain of GATA4 and C/H-3 domain of p300, respectively. Immunoprecipitation followed by western blotting demonstrated that RbAp48/46 repressed p300-induced acetylation of GATA4 and histones. While overexpressions of RbAp48/46 inhibited p300/GATA4-induced atrial natriuretic factors (ANF) and endotheline-1 (ET-1) promoter activities, knockdown of neither RbAp48 nor RbAp46 by RNAi enhanced these promoter activities in HEK293 cells. Stimulation of cardiomyocytes with phenylephrine (PE) decreased the binding of GATA4/p300 with RbAp48/46. RbAp48/46 repressed PE-induced hypertrophic responses such as myofibrillar organization, increase in cell size and promoter activation of the ANF and ET-1 in cardiomyocytes. Conclusion: These findings demonstrate that RbAp48 and RbAp46 form a functional protein complex with GATA4/p300 and regulated hypertrophic responses in cardiomyocytes.



1999 ◽  
Vol 112 (7) ◽  
pp. 1045-1054 ◽  
Author(s):  
P. Collas ◽  
M.R. Liang ◽  
M. Vincent ◽  
P. Alestrom

We have investigated the functional organization of active and silent integrated luciferase transgenes in zebrafish, with the aim of accounting for the variegation of transgene expression in this species. We demonstrate the enrichment of transcriptionally active transgenes in acetylated histone H4 and the dynamic association of the transgenes with splicing factor SC35 and RNA Pol II. Analysis of interphase nuclei and extended chromatin fibers by immunofluorescence and in situ hybridization reveals a co-localization of transgenes with acetylated H4 in luciferase-expressing animals only. Enrichment of expressed transgenes in acetylated H4 is further demonstrated by their co-precipitation from chromatin using anti-acetylated H4 antibodies. Little correlation exists, however, between the level of histone acetylation and the degree of transgene expression. In transgene-expressing zebrafish, most transgenes co-localize with Pol II and SC35, whereas no such association occurs in non-expressing individuals. Inhibition of Pol II abolishes transgene expression and disrupts association of transgenes with SC35, although inactivated transgenes remains enriched in acetylated histones. Exposure of embryos to the histone deacetylation inhibitor TSA induces expression of most silent transgenes. Chromatin containing activated transgenes becomes enriched in acetylated histones and the transgenes recruit SC35 and Pol II. The results demonstrate a correlation between H4 acetylation and transgene activity, and argue that active transgenes dynamically recruit splicing factors and Pol II. The data also suggest that dissociation of splicing factors from transgenes upon Pol II inhibition is not a consequence of changes in H4 acetylation.



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