scholarly journals Rsc4 Connects the Chromatin Remodeler RSC to RNA Polymerases

2006 ◽  
Vol 26 (13) ◽  
pp. 4920-4933 ◽  
Author(s):  
Julie Soutourina ◽  
Véronique Bordas-Le Floch ◽  
Gabrielle Gendrel ◽  
Amando Flores ◽  
Cécile Ducrot ◽  
...  

ABSTRACT RSC is an essential, multisubunit chromatin remodeling complex. We show here that the Rsc4 subunit of RSC interacted via its C terminus with Rpb5, a conserved subunit shared by all three nuclear RNA polymerases (Pol). Furthermore, the RSC complex coimmunoprecipitated with all three RNA polymerases. Mutations in the C terminus of Rsc4 conferred a thermosensitive phenotype and the loss of interaction with Rpb5. Certain thermosensitive rpb5 mutations were lethal in combination with an rsc4 mutation, supporting the physiological significance of the interaction. Pol II transcription of ca. 12% of the yeast genome was increased or decreased twofold or more in a rsc4 C-terminal mutant. The transcription of the Pol III-transcribed genes SNR6 and RPR1 was also reduced, in agreement with the observed localization of RSC near many class III genes. Rsc4 C-terminal mutations did not alter the stability or assembly of the RSC complex, suggesting an impact on Rsc4 function. Strikingly, a C-terminal mutation of Rsc4 did not impair RSC recruitment to the RSC-responsive genes DUT1 and SMX3 but rather changed the chromatin accessibility of DNases to their promoter regions, suggesting that the altered transcription of DUT1 and SMX3 was the consequence of altered chromatin remodeling.

Author(s):  
Yongpeng Jiang ◽  
Jie Huang ◽  
Kehuan Lun ◽  
Boyuan Li ◽  
Haonan Zheng ◽  
...  

AbstractBackgroundThe relationship between transcription and the 3D genome organization is one of the most important questions in molecular biology, but the roles of transcription in 3D chromatin remain controversial. Multiple groups showed that transcription affects global Cohesin binding and genome 3D structures. At the same time, several studies have indicated that transcription inhibition does not affect global chromatin interactions.ResultsHere, we provide the most comprehensive evidence to date to demonstrate that transcription plays a marginal role in organizing the 3D genome in mammalian cells: 1) degraded Pol I, Pol II and Pol III proteins in mESCs, and showed their loss results in little or no changes of global 3D chromatin structures for the first time; 2) selected RNA polymerases high abundance binding sites-associated interactions and found they still persist after the degradation; 3) generated higher resolution chromatin interaction maps and revealed that transcription inhibition mildly alters small loop domains; 4) identified Pol II bound but CTCF and Cohesin unbound loops and disclosed that they are largely resistant to transcription inhibition. Interestingly, Pol II depletion for a longer time significantly affects the chromatin accessibility and Cohesin occupancy, suggesting RNA polymerases are capable of affecting the 3D genome indirectly. So, the direct and indirect effects of transcription inhibition explain the previous confusing effects on the 3D genome.ConclusionsWe conclude that Pol I, Pol II, and Pol III loss only mildly alter chromatin interactions in mammalian cells, suggesting the 3D chromatin structures are pre-established and relatively stable.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Andrea Bogutzki ◽  
Natalie Naue ◽  
Lidia Litz ◽  
Andreas Pich ◽  
Ute Curth

Abstract During DNA replication in E. coli, a switch between DnaG primase and DNA polymerase III holoenzyme (pol III) activities has to occur every time when the synthesis of a new Okazaki fragment starts. As both primase and the χ subunit of pol III interact with the highly conserved C-terminus of single-stranded DNA-binding protein (SSB), it had been proposed that the binding of both proteins to SSB is mutually exclusive. Using a replication system containing the origin of replication of the single-stranded DNA phage G4 (G4ori) saturated with SSB, we tested whether DnaG and pol III can bind concurrently to the primed template. We found that the addition of pol III does not lead to a displacement of primase, but to the formation of higher complexes. Even pol III-mediated primer elongation by one or several DNA nucleotides does not result in the dissociation of DnaG. About 10 nucleotides have to be added in order to displace one of the two primase molecules bound to SSB-saturated G4ori. The concurrent binding of primase and pol III is highly plausible, since even the SSB tetramer situated directly next to the 3′-terminus of the primer provides four C-termini for protein-protein interactions.


2021 ◽  
Vol 11 (9) ◽  
pp. 3770
Author(s):  
Monica Tatarciuc ◽  
George Alexandru Maftei ◽  
Anca Vitalariu ◽  
Ionut Luchian ◽  
Ioana Martu ◽  
...  

Inlay-retained dental bridges can be a viable minimally invasive alternative when patients reject the idea of implant therapy or conventional retained full-coverage fixed dental prostheses, which require more tooth preparation. Inlay-retained dental bridges are indicated in patients with good oral hygiene, low susceptibility to caries, and a minimum coronal tooth height of 5 mm. The present study aims to evaluate, through the finite element method (FEM), the stability of these types of dental bridges and the stresses on the supporting teeth, under the action of masticatory forces. The analysis revealed the distribution of the load on the bridge elements and on the retainers, highlighting the areas of maximum pressure. The results of our study demonstrate that the stress determined by the loading force cannot cause damage to the prosthetic device or to abutment teeth. Thus, it can be considered an optimal economical solution for treating class III Kennedy edentation in young patients or as a provisional pre-implant rehabilitation option. However, special attention must be paid to its design, especially in the connection area between the bridge elements, because the connectors and the retainers represent the weakest parts.


1994 ◽  
Vol 14 (3) ◽  
pp. 2147-2158
Author(s):  
R J Maraia ◽  
D J Kenan ◽  
J D Keene

Ample evidence indicates that Alu family interspersed elements retrotranspose via primary transcripts synthesized by RNA polymerase III (pol III) and that this transposition sometimes results in genetic disorders in humans. However, Alu primary transcripts can be processed posttranscriptionally, diverting them away from the transposition pathway. The pol III termination signal of a well-characterized murine B1 (Alu-equivalent) element inhibits RNA 3' processing, thereby stabilizing the putative transposition intermediary. We used an immobilized template-based assay to examine transcription termination by VA1, 7SL, and Alu class III templates and the role of transcript release in the pol III terminator-dependent inhibition of processing of B1-Alu transcripts. We found that the RNA-binding protein La confers this terminator-dependent 3' processing inhibition on transcripts released from the B1-Alu template. Using pure recombinant La protein and affinity-purified transcription complexes, we also demonstrate that La facilitates multiple rounds of transcription reinitiation by pol III. These results illustrate an important role for La in RNA production by demonstrating its ability to clear the termination sites of class III templates, thereby promoting efficient use of transcription complexes by pol III. The role of La as a potential regulatory factor in transcript maturation and how this might apply to Alu interspersed elements is discussed.


2012 ◽  
Vol 17 (6) ◽  
pp. 41-51 ◽  
Author(s):  
Fernando Antonio Gonçalves ◽  
Vânia Célia Vieira de Siqueira

OBJECTIVE: To evaluate the stability of bimaxillary surgery in patients with skeletal malocclusion, with the use of rigid internal fixation. METHODS: Lateral cephalograms from 20 patients, 11 males and 9 females, mean age of 26 years and 1 month, were evaluated before surgery, immediately post-operative and at least 6 months after surgery. Nineteen cephalometric measurements were evaluated, and the results were statistically analyzed by means of the Student's t test and the Kruskal-Wallis test. RESULTS: The Le Fort I maxillary advancement surgery showed almost no relapse. There was lack of stability of mandibular setback, with relapse of 37.33% on point B, due to counterclockwise rotation of the mandible between post-operative periods, occurred by better intercuspation after surgery and muscle adaptation. The results showed the same tendencies for both genders. CONCLUSION: It was concluded that on the bimaxillary surgery treatment of Class III malocclusion, the maxillary surgery was very stable, but the mandibular setback recurred. No statistical differences were found in surgical stability between genders.


2019 ◽  
Vol 9 ◽  
pp. 59-64
Author(s):  
Ramesh Agrawal ◽  
Dolly P. Patel ◽  
Bhagyashree B. Desai

The current paper depicts the challenges faced during the treatment of a complicated case of mandibular condylar head fracture, facial asymmetry, and centric relation-centric occlusion (CR-CO) discrepancy along with Class III malocclusion. A 20-year-old female reported with the chief complaint of difficulty in chewing and concern with her appearance due to deviated jaw and had a history of trauma over chin region. The clinical and radiographic examination revealed significant facial asymmetry with long face, right-sided deviation of the mandible, fractured condyle, CR-CO discrepancy, cross- bite with Class III malocclusion, and a missing mandibular single incisor along with non-vital 21 and 22. She was treated with 0.022 MBT appliance along with guiding plane for CR-CO correction followed by asymmetric bilateral sagittal split osteotomy and differential set back on the right and left sides and finally rigid fixation. A good facial profile and functional occlusion were achieved and non-vital 21 and 22 were esthetically rehabilitated with PFM crowns. The stability of surgical as well as orthodontic corrections was excellent and appreciable in the records obtained 2-year post-treatment. When faced with mutilated malocclusion, with multiple problems, sequential correction of functional malocclusion with dental decompensation followed by skeletal correction with surgical approach has yielded a appreciable facial correction with good stability showing 2-year post-treatment follow-up.


2010 ◽  
Vol 30 (13) ◽  
pp. 3176-3186 ◽  
Author(s):  
Chandrashekara Mallappa ◽  
Brian T. Nasipak ◽  
Letitiah Etheridge ◽  
Elliot J. Androphy ◽  
Stephen N. Jones ◽  
...  

ABSTRACT Knockdown of the Brg1 ATPase subunit of SWI/SNF chromatin remodeling enzymes in developing zebrafish caused stunted tail formation and altered sarcomeric actin organization, which phenocopies the loss of the microRNA processing enzyme Dicer, or the knockdown of myogenic microRNAs. Furthermore, myogenic microRNA expression and differentiation was blocked in Brg1 conditional myoblasts differentiated ex vivo. The binding of Brg1 upstream of myogenic microRNA sequences correlated with MyoD binding and accessible chromatin structure in satellite cells and myofibers, and it was required for chromatin accessibility and microRNA expression in a tissue culture model for myogenesis. The results implicate ATP-dependent chromatin remodelers in myogenic microRNA gene regulation.


Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 58
Author(s):  
Jérôme Archambeau ◽  
Alice Blondel ◽  
Rémy Pedeux

The ING family of tumor suppressor genes is composed of five members (ING1-5) involved in cell cycle regulation, DNA damage response, apoptosis and senescence. All ING proteins belong to various HAT or HDAC complexes and participate in chromatin remodeling that is essential for genomic stability and signaling pathways. The gatekeeper functions of the INGs are well described by their role in the negative regulation of the cell cycle, notably by modulating the stability of p53 or the p300 HAT activity. However, the caretaker functions are described only for ING1, ING2 and ING3. This is due to their involvement in DNA repair such as ING1 that participates not only in NERs after UV-induced damage, but also in DSB repair in which ING2 and ING3 are required for accumulation of ATM, 53BP1 and BRCA1 near the lesion and for the subsequent repair. This review summarizes evidence of the critical roles of ING proteins in cell cycle regulation and DNA repair to maintain genomic stability.


Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2038
Author(s):  
Rada Amin ◽  
Kaushlendra Tripathi ◽  
Ralph D. Sanderson

Heparanase (HPSE) is an endoglycosidase that cleaves heparan sulfate and has been shown in various cancers to promote metastasis, angiogenesis, osteolysis, and chemoresistance. Although heparanase is thought to act predominantly extracellularly or within the cytoplasm, it is also present in the nucleus, where it may function in regulating gene transcription. Using myeloma cell lines, we report here that heparanase enhances chromatin accessibility and confirm a previous report that it also upregulates the acetylation of histones. Employing the Multiple Myeloma Research Foundation CoMMpass database, we demonstrate that patients expressing high levels of heparanase display elevated expression of proteins involved in chromatin remodeling and several oncogenic factors compared to patients expressing low levels of heparanase. These signatures were consistent with the known function of heparanase in driving tumor progression. Chromatin opening and downstream target genes were abrogated by inhibition of heparanase. Enhanced levels of heparanase in myeloma cells led to a dramatic increase in phosphorylation of PTEN, an event known to stabilize PTEN, leading to its inactivity and loss of tumor suppressor function. Collectively, this study demonstrates that heparanase promotes chromatin opening and transcriptional activity, some of which likely is through its impact on diminishing PTEN tumor suppressor activity.


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