scholarly journals Chromatin Modifiers in Transcriptional Regulation: New Findings and Prospects

Acta Naturae ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 16-30
Author(s):  
Marina Yu. Mazina ◽  
Nadezhda E. Vorobyeva
Keyword(s):  
Rna Polymerase Ii ◽  
Transcriptional Activation ◽  
Catalytic Subunits ◽  
Chromatin Remodelers ◽  
Functional Activities ◽  
Current Trends ◽  
New Findings ◽  
Eukaryotic Gene ◽  
Histone Modifiers ◽  
Chromatin Modifiers

Histone-modifying and remodeling complexes are considered the main coregulators that affect transcription by changing the chromatin structure. Coordinated action by these complexes is essential for the transcriptional activation of any eukaryotic gene. In this review, we discuss current trends in the study of histone modifiers and chromatin remodelers, including the functional impact of transcriptional proteins/complexes i.e., pioneers; remodeling and modification of non-histone proteins by transcriptional complexes; the supplementary functions of the non-catalytic subunits of remodelers, and the participation of histone modifiers in the pause of RNA polymerase II. The review also includes a scheme illustrating the mechanisms of recruitment of the main classes of remodelers and chromatin modifiers to various sites in the genome and their functional activities.

Co-dependent recruitment of Ino80p and Snf2p is required for yeast CUP1 activation

2014 ◽  
Vol 92 (1) ◽  
pp. 69-75 ◽  
Author(s):  
Roshini N. Wimalarathna ◽  
Po Yun Pan ◽  
Chang-Hui Shen
Keyword(s):  
Rna Polymerase ◽  
Histone Acetylation ◽  
Rna Polymerase Ii ◽  
Chromatin Remodeling ◽  
Transcriptional Activation ◽  
Copper Toxicity ◽  
Yeast Cells ◽  
Chromatin Remodelers ◽  
Insight Into ◽  
Cup1 Promoter

In yeast, Ace1p-dependent induction of CUP1 is responsible for protecting cells from copper toxicity. Although the mechanism of yeast CUP1 induction has been studied intensively, it is still uncertain which chromatin remodelers are involved in CUP1 transcriptional activation. Here, we show that yeast cells are inviable in the presence of copper when either chromatin remodeler, Ino80p or Snf2p, is not present. This inviability is due to the lack of CUP1 expression in ino80Δ and snf2Δ cells. Subsequently, we observe that both Ino80p and Snf2p are present at the promoter and they are responsible for recruiting chromatin remodeling activity to the CUP1 promoter under induced conditions. These results suggest that they directly participate in CUP1 transcriptional activation. Furthermore, the codependent recruitment of both INO80 and SWI/SNF depends on the presence of the transcriptional activator, Ace1p. We also demonstrate that both remodelers are required to recruit RNA polymerase II and targeted histone acetylation, indicating that remodelers are recruited to the CUP1 promoter before RNA polymerase II and histone acetylases. These observations provide evidence for the mechanism of CUP1 induction. As such, we propose a model that describes novel insight into the order of events in CUP1 activation.

scholarly journals Histone chaperone Nucleophosmin regulates transcription of key genes involved in oral tumorigenesis

2019 ◽  
Author(s):  
Parijat Senapati ◽  
Suchismita Dey ◽  
Deepthi Sudarshan ◽  
Aditya Bhattacharya ◽  
Shyla G ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Transcriptional Activation ◽  
Histone Chaperone ◽  
Migration And Invasion ◽  
Chromatin Remodelers ◽  
Hypersensitive Sites ◽  
Active Transcription ◽  
Key Genes ◽  
Oral Cancer Cells ◽  
In Cells

ABSTRACTNucleophosmin (NPM1) is a multifunctional histone chaperone that can activate RNA Polymerase II-driven chromatin transcription. Acetylation of NPM1 by acetyltransferase p300 has been shown to further enhance its transcription activation potential. Moreover, its total and acetylated pools are increased in oral squamous cell carcinoma. However, the role of NPM1 or its acetylated form (AcNPM1) in transcriptional regulation in cells is not fully elucidated. Using ChIP-seq analyses, we show that AcNPM1 co-occupies marks of active transcription at promoters and DNase I hypersensitive sites at enhancers. Moreover, NPM1 interacts with proteins involved in transcription, including RNA Pol II, general transcription factors, mediator subunits, histone acetyltransferase complexes, and chromatin remodelers. Moreover, its histone chaperone also contributes to transcriptional activation. We further show that AcNPM1 regulates key genes required for proliferation, migration and invasion potential of oral cancer cells and knockdown of NPM1 mitigates these processes in cells as well as orthotopic tumors in mice. Collectively, these results establish that AcNPM1 functions as a coactivator and regulates the expression of key genes involved in oral tumorigenesis.

scholarly journals The Non-Canonical Aspects of MicroRNAs: Many Roads to Gene Regulation

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1465 ◽  
Author(s):  
Christiaan J. Stavast ◽  
Stefan J. Erkeland
Keyword(s):  
Rna Polymerase Ii ◽  
Transcriptional Activation ◽  
Small Rnas ◽  
Target Genes ◽  
Biological Functions ◽  
Rnase Iii ◽  
Mrna Targets ◽  
Argonaute Proteins ◽  
Epigenetic Modifiers ◽  
Encoding Genes

MicroRNAs (miRNAs) are critical regulators of gene expression. As miRNAs are frequently deregulated in many human diseases, including cancer and immunological disorders, it is important to understand their biological functions. Typically, miRNA-encoding genes are transcribed by RNA Polymerase II and generate primary transcripts that are processed by RNase III-endonucleases DROSHA and DICER into small RNAs of approximately 21 nucleotides. All miRNAs are loaded into Argonaute proteins in the RNA-induced silencing complex (RISC) and act as post-transcriptional regulators by binding to the 3′- untranslated region (UTR) of mRNAs. This seed-dependent miRNA binding inhibits the translation and/or promotes the degradation of mRNA targets. Surprisingly, recent data presents evidence for a target-mediated decay mechanism that controls the level of specific miRNAs. In addition, several non-canonical miRNA-containing genes have been recently described and unexpected functions of miRNAs have been identified. For instance, several miRNAs are located in the nucleus, where they are involved in the transcriptional activation or silencing of target genes. These epigenetic modifiers are recruited by RISC and guided by miRNAs to specific loci in the genome. Here, we will review non-canonical aspects of miRNA biology, including novel regulators of miRNA expression and functions of miRNAs in the nucleus.

scholarly journals Cockayne syndrome B protein acts as an ATP-dependent processivity factor that helps RNA polymerase II overcome nucleosome barriers

2020 ◽  
Vol 117 (41) ◽  
pp. 25486-25493 ◽  
Author(s):  
Jun Xu ◽  
Wei Wang ◽  
Liang Xu ◽  
Jia-Yu Chen ◽  
Jenny Chong ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Neurological Diseases ◽  
Transcription Elongation ◽  
Cockayne Syndrome ◽  
Stable Complex ◽  
Loss Of Function ◽  
Pol Ii ◽  
Chromatin Remodelers ◽  
Processivity Factor

While loss-of-function mutations in Cockayne syndrome group B protein (CSB) cause neurological diseases, this unique member of the SWI2/SNF2 family of chromatin remodelers has been broadly implicated in transcription elongation and transcription-coupled DNA damage repair, yet its mechanism remains largely elusive. Here, we use a reconstituted in vitro transcription system with purified polymerase II (Pol II) and Rad26, a yeast ortholog of CSB, to study the role of CSB in transcription elongation through nucleosome barriers. We show that CSB forms a stable complex with Pol II and acts as an ATP-dependent processivity factor that helps Pol II across a nucleosome barrier. This noncanonical mechanism is distinct from the canonical modes of chromatin remodelers that directly engage and remodel nucleosomes or transcription elongation factors that facilitate Pol II nucleosome bypass without hydrolyzing ATP. We propose a model where CSB facilitates gene expression by helping Pol II bypass chromatin obstacles while maintaining their structures.

scholarly journals Current trends in leather science

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Anthony D. Covington ◽  
William R. Wise
Keyword(s):  
Ionic Liquids ◽  
Potential Role ◽  
Solid Medium ◽  
Leather Industry ◽  
Chromium Vi ◽  
Current Trends ◽  
New Findings ◽  
Vegetable Tanning ◽  
Sulfide Species

Abstract In preparing the second edition of ‘Tanning Chemistry. The Science of Leather.’, the literature was updated and the content was revised and reviewed. Here, the new findings are presented and discussed. Notable developments include the necessary rethinking of the mechanism of sulfide unhairing because of new understanding of the aqueous chemistry of sulfide species. Revision upwards of the value of the second pKa for sulfide species ionisation means that S2− cannot exist in an aqueous medium, so the unhairing species in hair burn reactions is HS−. Although the technology remains the same, this means the mechanisms of associated reactions such as immunisation must be revised. Rawstock preservation has benefitted from studies of the potential role of materials from plants which accumulate salt, but which also contribute terpene compounds. There is also further discussion on the continuing issue of chromium (VI) in the leather industry. The application to processing of new solvents, ionic liquids and deep eutectics, is the coming technology, which offers transforming options for new chemistries and products. Renewed interest in vegetable tanning and methods of wet white processing are current trends. Also, within the topic of reagent delivery is processing in a solid medium of plastic beads. Graphical abstract

scholarly journals The Landscape of Signaling Pathways and Proteasome Inhibitors Combinations in Multiple Myeloma

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1235
Author(s):  
Tina Paradzik ◽  
Cecilia Bandini ◽  
Elisabetta Mereu ◽  
Maria Labrador ◽  
Elisa Taiana ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Signaling Pathways ◽  
Plasma Cells ◽  
Proteasome Inhibitors ◽  
Treatment Resistance ◽  
Positive Outcome ◽  
Chromatin Remodelers ◽  
Histone Modifiers ◽  
Substantial Progress ◽  
Immune Dysfunctions

Multiple myeloma is a malignancy of terminally differentiated plasma cells, characterized by an extreme genetic heterogeneity that poses great challenges for its successful treatment. Due to antibody overproduction, MM cells depend on the precise regulation of the protein degradation systems. Despite the success of PIs in MM treatment, resistance and adverse toxic effects such as peripheral neuropathy and cardiotoxicity could arise. To this end, the use of rational combinatorial treatments might allow lowering the dose of inhibitors and therefore, minimize their side-effects. Even though the suppression of different cellular pathways in combination with proteasome inhibitors have shown remarkable anti-myeloma activities in preclinical models, many of these promising combinations often failed in clinical trials. Substantial progress has been made by the simultaneous targeting of proteasome and different aspects of MM-associated immune dysfunctions. Moreover, targeting deranged metabolic hubs could represent a new avenue to identify effective therapeutic combinations with PIs. Finally, epigenetic drugs targeting either DNA methylation, histone modifiers/readers, or chromatin remodelers are showing pleiotropic anti-myeloma effects alone and in combination with PIs. We envisage that the positive outcome of patients will probably depend on the availability of more effective drug combinations and treatment of early MM stages. Therefore, the identification of sensitive targets and aberrant signaling pathways is instrumental for the development of new personalized therapies for MM patients.

RNA polymerase II cofactor PC2 facilitates activation of transcription by GAL4-AH in vitro

1994 ◽  
Vol 14 (6) ◽  
pp. 3927-3937
Author(s):  
M Kretzschmar ◽  
G Stelzer ◽  
R G Roeder ◽  
M Meisterernst
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcriptional Activation ◽  
Activation Domains ◽  
Positive Effects ◽  
Activation Of Transcription ◽  
Transcriptional Activation Domains ◽  
Necessary And Sufficient ◽  
Specific Pathway

We have isolated from a crude Hela cell cofactor fraction (USA) a novel positive cofactor that cooperates with the general transcription machinery to effect efficient stimulation of transcription by GAL4-AH, a derivative of the Saccharomyces cerevisiae regulatory factor GAL4. PC2 was shown to be a 500-kDa protein complex and to be functionally and biochemically distinct from native TFIID and previously identified cofactors. In the presence of native TFIID and other general factors, PC2 was necessary and sufficient for activation by GAL4-AH. Cofactor function was specific for transcriptional activation domains of GAL4-AH. The repressor histone H1 further potentiated but was not required for activation of transcription by GAL4-AH. On the basis of the observation that PC2 exerts entirely positive effects on transcription, we propose a model in which PC2 increases the activity of the preinitiation complex in the presence of an activator, thereby establishing a specific pathway during activation of RNA polymerase II.

scholarly journals The Swi/Snf Chromatin Remodeling Complex Is Required for Ribosomal DNA and Telomeric Silencing in Saccharomyces cerevisiae

2004 ◽  
Vol 24 (18) ◽  
pp. 8227-8235 ◽  
Author(s):  
Vardit Dror ◽  
Fred Winston
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Chromatin Remodeling ◽  
Ribosomal Dna ◽  
Transcriptional Activation ◽  
Rdna Locus ◽  
Detectable Effect ◽  
Chromatin Remodeling Complex ◽  
Two Factors

ABSTRACT The Swi/Snf chromatin remodeling complex has been previously demonstrated to be required for transcriptional activation and repression of a subset of genes in Saccharomyces cerevisiae. In this work we demonstrate that Swi/Snf is also required for repression of RNA polymerase II-dependent transcription in the ribosomal DNA (rDNA) locus (rDNA silencing). This repression appears to be independent of both Sir2 and Set1, two factors known to be required for rDNA silencing. In contrast to many other rDNA silencing mutants that have elevated levels of rDNA recombination, snf2Δ mutants have a significantly decreased level of rDNA recombination. Additional studies have demonstrated that Swi/Snf is also required for silencing of genes near telomeres while having no detectable effect on silencing of HML or HMR.

scholarly journals Independent Recruitment of Mediator and SAGA by the Activator Met4

2006 ◽  
Vol 26 (8) ◽  
pp. 3149-3163 ◽  
Author(s):  
Christophe Leroy ◽  
Laëtitia Cormier ◽  
Laurent Kuras
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Rna Polymerase Ii ◽  
Gene Network ◽  
Pol Ii ◽  
Eukaryotic Gene Expression ◽  
Eukaryotic Gene ◽  
Target Promoters ◽  
Sulfur Containing

ABSTRACT Mediator is a key RNA polymerase II (Pol II) cofactor in the regulation of eukaryotic gene expression. It is believed to function as a coactivator linking gene-specific activators to the basal Pol II initiation machinery. In support of this model, we provide evidence that Mediator serves in vivo as a coactivator for the yeast activator Met4, which controls the gene network responsible for the biosynthesis of sulfur-containing amino acids and S-adenosylmethionine. In addition, we show that SAGA (Spt-Ada-Gcn5-acetyltransferase) is also recruited to Met4 target promoters, where it participates in the recruitment of Pol II by a mechanism involving histone acetylation. Interestingly, we find that SAGA is not required for Mediator recruitment by Met4 and vice versa. Our results provide a novel example of functional interplay between Mediator and coactivators involved in histone modification.

scholarly journals Mediator subunit MED1 is required for E2A-PBX1–mediated oncogenic transcription and leukemic cell growth

2021 ◽  
Vol 118 (6) ◽  
pp. e1922864118 ◽  
Author(s):  
Yu-Ling Lee ◽  
Keiichi Ito ◽  
Wen-Chieh Pi ◽  
I-Hsuan Lin ◽  
Chi-Shuen Chu ◽  
...  
Keyword(s):  
Cell Growth ◽  
Rna Polymerase Ii ◽  
Transcriptional Activation ◽  
Critical Role ◽  
Gene Activation ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Specific Gene ◽  
Aberrant Expression ◽  
Transcriptional Machinery

The chimeric transcription factor E2A-PBX1, containing the N-terminal activation domains of E2A fused to the C-terminal DNA-binding domain of PBX1, results in 5% of pediatric acute lymphoblastic leukemias (ALL). We recently have reported a mechanism for RUNX1-dependent recruitment of E2A-PBX1 to chromatin in pre-B leukemic cells; but the subsequent E2A-PBX1 functions through various coactivators and the general transcriptional machinery remain unclear. The Mediator complex plays a critical role in cell-specific gene activation by serving as a key coactivator for gene-specific transcription factors that facilitates their function through the RNA polymerase II transcriptional machinery, but whether Mediator contributes to aberrant expression of E2A-PBX1 target genes remains largely unexplored. Here we show that Mediator interacts directly with E2A-PBX1 through an interaction of the MED1 subunit with an E2A activation domain. Results of MED1 depletion by CRISPR/Cas9 further indicate that MED1 is specifically required for E2A-PBX1–dependent gene activation and leukemic cell growth. Integrated transcriptome and cistrome analyses identify pre-B cell receptor and cell cycle regulatory genes as direct cotargets of MED1 and E2A-PBX1. Notably, complementary biochemical analyses also demonstrate that recruitment of E2A-PBX1 to a target DNA template involves a direct interaction with DNA-bound RUNX1 that can be further stabilized by EBF1. These findings suggest that E2A-PBX1 interactions with RUNX1 and MED1/Mediator are of functional importance for both gene-specific transcriptional activation and maintenance of E2A-PBX1–driven leukemia. The MED1 dependency for E2A-PBX1–mediated gene activation and leukemogenesis may provide a potential therapeutic opportunity by targeting MED1 in E2A-PBX1+ pre-B leukemia.

Sign in / Sign up

Export Citation Format

Share Document