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Studies On The Role Of Enhancer Rnas In The Release Of Rna Polymerase Ii From Promoter Proximal Pausing
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Book Synopsis Studies on the Role of Enhancer RNAs in the Release of RNA Polymerase II from Promoter-proximal Pausing by : Vladyslava Gorbovytska
Download or read book Studies on the Role of Enhancer RNAs in the Release of RNA Polymerase II from Promoter-proximal Pausing written by Vladyslava Gorbovytska and published by . This book was released on 2021 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Factors Controlling Promoter-proximal Pausing by RNA Polymerase II by : Nicholas James Fuda
Download or read book Factors Controlling Promoter-proximal Pausing by RNA Polymerase II written by Nicholas James Fuda and published by . This book was released on 2012 with total page 202 pages. Available in PDF, EPUB and Kindle. Book excerpt: Most gene expression is regulated at the level of transcription, and the transition from initiation to productive elongation is a key point of regulation. This transition is accompanied by pausing of transcriptionally engaged polymerase in the promoter-proximal region of several heat shock genes. Although this mechanism of regulation was long thought to be limited to a few genes, recent evidence has indicated that pausing is wide-spread in higher eukaryotes. Therefore, it is increasingly important to understand the mechanisms controlling the paused polymerase. I have investigated how the site of pausing on Hsp70 is specified using highresolution mapping of polymerase on reporter genes with shifted pausing site sequences. The results indicate that the downstream sequence dictates pause position and the overall level of pausing. I have also used RNAi knock-down in Drosophila cell culture to study the roles of several factors in establishing, maintaining, and releasing the paused polymerase. These experiments have shown GAGA factor is required for pausing on many of its target genes, and the knock-down effects indicate it is involved in establishing the pause. In contrast, Spt5, a protein previously shown to enhance pausing in vitro, reduces pausing genome-wide by increasing levels of elongating polymerase. Two kinases, P-TEFb and CDK12, function in productive elongation. Previously our lab showed that P-TEFb inhibition prevented the transition into elongation, limiting the polymerase to the 5' end of the heat shock-induced Hsp70 gene. I mapped these polymerases in high resolution to show they occupied sites further downstream than the normal pause sites, suggesting P-TEFb activity may not solely release the paused polymerase. I also determined the localization of CDK12 on active genes. Its localization downstream of P-TEFb suggests that these kinases may have distinct functions. Finally, I have examined the role of Fcp1 in Hsp70 transcription. Our lab previously showed the CTD phosphatase Fcp1 was required for optimum expression of Hsp70 mRNA. Fcp1 knock-down reduced the heat shock levels of Pol II and increased phosphorylation of nonchromatin bound Pol II, indicating that Fcp1 recycling of RNA polymerase II to an initiationcompetent form is required for optimal Hsp70 heat shock transcription.
Book Synopsis Fnctional Evolution of Promoter-proximal Pausing Factors in the Regulation of RNA Polymerase II Transcription by : Gregory T. Booth
Download or read book Fnctional Evolution of Promoter-proximal Pausing Factors in the Regulation of RNA Polymerase II Transcription written by Gregory T. Booth and published by . This book was released on 2018 with total page 404 pages. Available in PDF, EPUB and Kindle. Book excerpt: Promoter-proximal pausing of RNA Polymerase II (Pol II) is now recognized as a ubiquitous mechanism for regulating gene expression in metazoans. By capturing engaged Pol II shortly after transcription initiation, genes are primed for activation of RNA synthesis, enabling cells to rapidly alter global transcription programs. However, despite conservation of many factors involved in establishing this regulatory platform, many eukaryotes do not control gene expression through this process. Here, the examination of the global transcriptional landscape in two distantly related yeast revealed unprecedented divergence in Pol II distributions across genes. Previously undescribed pause-like profiles were identified within promoter-proximal regions of the fission yeast, Schizosaccharomyces pombe, that are sensitive to loss of the conserved elongation factor, Spt4. Thus, fission yeast might employ a variant of the system of regulation found in higher eukaryotes In flies and mammals, Pol II arrested within the promoter proximal region of a gene can only be released through the activity of a positive-transcription elongation factor (P-TEFb), composed of kinase (Cdk9) and cyclin (CycT1/2) subunits. Investigating the functional impact of Cdk9 on transcription in fission yeast revealed that, unlike most metazoan systems, Pol II in S. pombe is capable of overcoming the early elongation barrier after kinase inhibition, although not without consequence. However, fission yeast lack the metazoan-specific negative elongation factor complex (NELF) involved in pausing, perhaps limiting their ability to control the release of Pol II through phosphorylation of the elongation complex. Ultimately, by depleting pausing factors from cell lines derived from Drosophila melanogaster, it was tested whether NELF is required for P-TEFb-regulated pause escape. While global transcription is largely unaffected by the loss of NELF, upon inhibition of Cdk9, a significant amount of Pol II is aberrantly released from the pause, suggesting reduced control of this regulation. These findings suggest that NELF may have evolutionarily refined an ancestral promoter-proximal architecture of the transcription elongation complex, giving rise to a novel mechanism for gene regulation.
Book Synopsis Regulation of Transcription Through RNA Polymerase II Promoter-proximal Pausing by : Melodi Damla Tastemel
Download or read book Regulation of Transcription Through RNA Polymerase II Promoter-proximal Pausing written by Melodi Damla Tastemel and published by . This book was released on 2018 with total page 100 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis RNA Exosome by : Torben Heick Jensen
Download or read book RNA Exosome written by Torben Heick Jensen and published by Springer Science & Business Media. This book was released on 2011-06-29 with total page 161 pages. Available in PDF, EPUB and Kindle. Book excerpt: The diversity of RNAs inside living cells is amazing. We have known of the more “classic” RNA species: mRNA, tRNA, rRNA, snRNA and snoRNA for some time now, but in a steady stream new types of molecules are being described as it is becoming clear that most of the genomic information of cells ends up in RNA. To deal with the enormous load of resulting RNA processing and degradation reactions, cells need adequate and efficient molecular machines. The RNA exosome is arising as a major facilitator to this effect. Structural and functional data gathered over the last decade have illustrated the biochemical importance of this multimeric complex and its many co-factors, revealing its enormous regulatory power. By gathering some of the most prominent researchers in the exosome field, it is the aim of this volume to introduce this fascinating protein complex as well as to give a timely and rich account of its many functions. The exosome was discovered more than a decade ago by Phil Mitchell and David Tollervey by its ability to trim the 3’end of yeast, S. cerevisiae, 5. 8S rRNA. In a historic account they laid out the events surrounding this identification and the subsequent birth of the research field. In the chapter by Kurt Januszyk and Christopher Lima the structural organization of eukaryotic exosomes and their evolutionary counterparts in bacteria and archaea are discussed in large part through presentation of structures.
Book Synopsis Introduction to Epigenetics by : Renato Paro
Download or read book Introduction to Epigenetics written by Renato Paro and published by Springer Nature. This book was released on 2021-03-23 with total page 215 pages. Available in PDF, EPUB and Kindle. Book excerpt: This open access textbook leads the reader from basic concepts of chromatin structure and function and RNA mechanisms to the understanding of epigenetics, imprinting, regeneration and reprogramming. The textbook treats epigenetic phenomena in animals, as well as plants. Written by four internationally known experts and senior lecturers in this field, it provides a valuable tool for Master- and PhD- students who need to comprehend the principles of epigenetics, or wish to gain a deeper knowledge in this field. After reading this book, the student will: Have an understanding of the basic toolbox of epigenetic regulation Know how genetic and epigenetic information layers are interconnected Be able to explain complex epigenetic phenomena by understanding the structures and principles of the underlying molecular mechanisms Understand how misregulated epigenetic mechanisms can lead to disease
Book Synopsis Dissection of the Precise Mechanisms of RNA Polymerase II Pausing and Elongation Using Nascent Transcript Analysis by : Hojoong Kwak
Download or read book Dissection of the Precise Mechanisms of RNA Polymerase II Pausing and Elongation Using Nascent Transcript Analysis written by Hojoong Kwak and published by . This book was released on 2013 with total page 183 pages. Available in PDF, EPUB and Kindle. Book excerpt: Limiting RNA polymerase II (Pol II) at various stages of the transcription cycle is critical for gene regulation, which often occurs during the elongation stage at promoter proximal pause sites and in gene bodies. To determine the distribution of Pol II along genes, I used nascent transcript analysis as a general method. First, I identified the precise positions of Pol II pausing near promoters using a genome-wide nuclear run-on, called Precision Run-On sequencing (PRO-seq) in Drosophila embryonic cells. Using this, I revealed how the position of pausing is associated with initiation and promoter DNA elements. To further dissect the precise dynamics of paused Pol II, I probed the stability of paused Pol II and its termination by analyzing steady-state turn-over of the nascent transcript associated with Drosophila Hsp70 promoter. This shows that paused Pol II on Hsp70 is stable for around 5 min and can either terminate or elongate into the gene body, which is consistent with optical measurements of paused Pol II. I also examined how Pol II elongates during the time course of rapid and robust inhibition of pause escape in mouse embryonic stem cells. The analysis of the elongation rates in nearly 1,000 genes showed tight interplay between promoter proximal pausing, early elongation rates, and co-transcriptional splicing at the beginning of the genes. Finally, I demonstrate that the nascent transcriptome analysis methods can be directly extended into mammalian tissues, and show possibility of linking the study of the fundamental mechanism of Pol II into biomedical applications.
Book Synopsis Promoter-proximal Pausing Mediated by the Exon Junction Complex Regulates Splicing by : Junaid Akhtar
Download or read book Promoter-proximal Pausing Mediated by the Exon Junction Complex Regulates Splicing written by Junaid Akhtar and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: Promoter-proximal pausing of RNA polymerase II (Pol II) is a widespread transcriptional regulatory step across metazoans. Here we find that the nuclear exon junction complex (pre-EJC) is a critical and conserved regulator of this process. Depletion of pre-EJC subunits leads to a global decrease in Pol II pausing and to premature entry into elongation. This effect occurs, at least in part, via non-canonical recruitment of pre-EJC components at promoters. Failure to recruit the pre-EJC at promoters results in increased binding of the positive transcription elongation complex (P-TEFb) and in enhanced Pol II release. Notably, restoring pausing is sufficient to rescue exon skipping and the photoreceptor differentiation defect associated with depletion of pre-EJC components in vivo. We propose that the pre-EJC serves as an early transcriptional checkpoint to prevent premature entry into elongation, ensuring proper recruitment of RNA processing components that are necessary for exon definition
Book Synopsis The Regulation of Premature Termination at Divergent Promoters by : Anthony Chun-yin Chiu
Download or read book The Regulation of Premature Termination at Divergent Promoters written by Anthony Chun-yin Chiu and published by . This book was released on 2017 with total page 221 pages. Available in PDF, EPUB and Kindle. Book excerpt: Transcription is one of the most fundamental processes in cells, governing the conversion of genetic information to RNA. Numerous regulatory mechanisms function to ensure that desired transcripts are being expressed. Promoters transcribe divergently, producing low-abundant upstream antisense RNAs (uaRNAs) in addition to a stable downstream RNAs. Thus, a central question is what mechanisms are sense RNAs more stable compared to most transcription events. It is proposed that an asymmetric distribution of Ul snRNP binding sites and polyadenylation site (PAS) motifs known as the UI-PAS axis regulates early termination of RNA Polymerase II. Here, we generated a conditional knockout of the essential RNA exosome subunit, Exosc3, in mouse embryonic stem cells. Removal of Exosc3 resulted in stabilization of polyadenylated uaRNAs, enhancer RNAs and long noncoding RNAs. In addition, promoter proximal pausing increased modestly upon Exosc3 removal. Interestingly, a large class of polyadenylated short transcripts in the sense direction terminate within the first intron, similar to premature termination observed upon Ul inhibition. Further investigation of these prematurely termination sites revealed they are found at the edges of stable nucleosome free regions demarcated by CpG islands and are suppressed by U1 snRNP. Interestingly, promoter-proximal Pol II pausing consists of two processes: TSS-proximal and +1 stable nucleosome pausing. Genes associated with premature termination have increased +1 stable nucleosome pausing, association of chromatin remodelers and are more sensitive to inhibition by flavopiridol or a Myc inhibitor. Additionally, the nuclear poly(A) binding protein, Pabpnl, promotes degradation of polyadenylated uaRNAs. Most Pabpnl sensitive uaRNAs are also Exosc3 substrates, and sensitivity to Pabpnl inhibition inversely correlates with the proximity of the termination site to the TSS. Interestingly, at uaRNAs and sense RNAs, Pabpnl -sensitive PAS termination events also occur near the first stable nucleosome, similar to Exosc3-sensitive PAS termination events, suggesting that Pabpnl collaborates with Exosc3 to regulate stability of polyadenylated transcripts. Hence, this supports a model whereby Ul snRNP, +1 stable nucleosomes and the degradation machinery converge to create a transcription elongation checkpoint downstream of promoter-proximal pausing.
Book Synopsis The Role of Spt5-nucleic Acid Contacts in Promoter Proximal Pausing of RNA Polymerase II. by : Roberta Dollinger
Download or read book The Role of Spt5-nucleic Acid Contacts in Promoter Proximal Pausing of RNA Polymerase II. written by Roberta Dollinger and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Promoter proximal pausing of RNA Polymerase II (Pol II) is a critical transcriptional regulatory mechanism in metazoans that requires DSIF and NELF. DSIF, composed of Spt4 and Spt5, establishes the pause by recruiting NELF to the elongation complex. However, the role of DSIF in pausing beyond NELF recruitment remains unclear. I used a highly purified in vitro system and Drosophila nuclear extract to investigate the role of DSIF in promoter proximal pausing. I identified two domains of Spt5, the KOW4 and NGN domains, that directly facilitate Pol II pausing. The KOW4 domain promotes pausing through its interaction with the nascent RNA while the NGN domain does so through a short alpha helical motif that is in close proximity to the non-transcribed DNA template strand. Mutation of this alpha helical motif in Drosophila has a male-specific dominant negative effect. The alpha helical motif is also needed to support fly viability. I also show that the interaction between the Spt5 KOW1 domain and the upstream DNA helix is required for DSIF association with the Pol II elongation complex and that DSIF-Pol II association is independent of the nascent transcript. Disruption of the KOW1-DNA interaction is dominant lethal in vivo. Finally, I show that the KOW2-3 domain of Spt5 mediates the recruitment of NELF to the elongation complex.
Book Synopsis Chromatin Regulation and Dynamics by : Anita Göndör
Download or read book Chromatin Regulation and Dynamics written by Anita Göndör and published by Academic Press. This book was released on 2016-10-25 with total page 498 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chromatin Regulation and Dynamics integrates knowledge on the dynamic regulation of primary chromatin fiber with the 3D nuclear architecture, then connects related processes to circadian regulation of cellular metabolic states, representing a paradigm of adaptation to environmental changes. The final chapters discuss the many ways chromatin dynamics can synergize to fundamentally contribute to the development of complex diseases. Chromatin dynamics, which is strategically positioned at the gene-environment interface, is at the core of disease development. As such, Chromatin Regulation and Dynamics, part of the Translational Epigenetics series, facilitates the flow of information between research areas such as chromatin regulation, developmental biology, and epidemiology by focusing on recent findings of the fast-moving field of chromatin regulation. Presents and discusses novel principles of chromatin regulation and dynamics with a cross-disciplinary perspective Promotes crosstalk between basic sciences and their applications in medicine Provides a framework for future studies on complex diseases by integrating various aspects of chromatin biology with cellular metabolic states, with an emphasis on the dynamic nature of chromatin and stochastic principles Integrates knowledge on the dynamic regulation of primary chromatin fiber with 3D nuclear architecture, then connects related processes to circadian regulation of cellular metabolic states, representing a paradigm of adaptation to environmental changes
Book Synopsis Untranslated Gene Regions and Other Non-coding Elements by : Lucy W. Barrett
Download or read book Untranslated Gene Regions and Other Non-coding Elements written by Lucy W. Barrett and published by Springer Science & Business Media. This book was released on 2013-06-26 with total page 63 pages. Available in PDF, EPUB and Kindle. Book excerpt: There is now compelling evidence that the complexity of higher organisms correlates with the relative amount of non-coding RNA rather than the number of protein-coding genes. Previously dismissed as “junk DNA”, it is the non-coding regions of the genome that are responsible for regulation, facilitating complex temporal and spatial gene expression through the combinatorial effect of numerous mechanisms and interactions working together to fine-tune gene expression. The major regions involved in regulation of a particular gene are the 5’ and 3’ untranslated regions and introns. In addition, pervasive transcription of complex genomes produces a variety of non-coding transcripts that interact with these regions and contribute to regulation. This book discusses recent insights into the regulatory roles of the untranslated gene regions and non-coding RNAs in the control of complex gene expression, as well as the implications of this in terms of organism complexity and evolution.
Download or read book HIV-1 Latency written by Guido Silvestri and published by Springer. This book was released on 2018-10-11 with total page 253 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume summarizes recent advances in understanding the mechanisms of HIV-1 latency, in characterizing residual viral reservoirs, and in developing targeted interventions to reduce HIV-1 persistence during antiretroviral therapy. Specific chapters address the molecular mechanisms that govern and regulate HIV-1 transcription and latency; assays and technical approaches to quantify viral reservoirs in humans and animal models; the complex interchange between viral reservoirs and the host immune system; computational strategies to model viral reservoir dynamics; and the development of therapeutic approaches that target viral reservoir cells. With contributions from an interdisciplinary group of investigators that cover a broad spectrum of subjects, from molecular virology to proof-of-principle clinical trials, this book is a valuable resource for basic scientists, translational investigators, infectious-disease physicians, individuals living with HIV/AIDS and the general public.
Book Synopsis Long Non Coding RNA Biology by : M.R.S. Rao
Download or read book Long Non Coding RNA Biology written by M.R.S. Rao and published by Springer. This book was released on 2017-08-16 with total page 336 pages. Available in PDF, EPUB and Kindle. Book excerpt: This contributed volume offers a comprehensive and detailed overview of the various aspects of long non-coding RNAs and discusses their emerging significance. Written by leading experts in the field, it motivates young researchers around the globe, and offers graduate and postgraduate students fascinating insights into genes and their regulation in eukaryotes and higher organisms.
Book Synopsis Epigenetic Gene Expression and Regulation by : Suming Huang
Download or read book Epigenetic Gene Expression and Regulation written by Suming Huang and published by Academic Press. This book was released on 2015-10-19 with total page 484 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetic Gene Expression and Regulation reviews current knowledge on the heritable molecular mechanisms that regulate gene expression, contribute to disease susceptibility, and point to potential treatment in future therapies. The book shows how these heritable mechanisms allow individual cells to establish stable and unique patterns of gene expression that can be passed through cell divisions without DNA mutations, thereby establishing how different heritable patterns of gene regulation control cell differentiation and organogenesis, resulting in a distinct human organism with a variety of differing cellular functions and tissues. The work begins with basic biology, encompasses methods, cellular and tissue organization, topical issues in epigenetic evolution and environmental epigenesis, and lastly clinical disease discovery and treatment. Each highly illustrated chapter is organized to briefly summarize current research, provide appropriate pedagogical guidance, pertinent methods, relevant model organisms, and clinical examples. Reviews current knowledge on the heritable molecular mechanisms that regulate gene expression, contribute to disease susceptibility, and point to potential treatment in future therapies Helps readers understand how epigenetic marks are targeted, and to what extent transgenerational epigenetic changes are instilled and possibly passed onto offspring Chapters are replete with clinical examples to empower the basic biology with translational significance Offers more than 100 illustrations to distill key concepts and decipher complex science
Book Synopsis Gene Regulatory Sequences and Human Disease by : Nadav Ahituv
Download or read book Gene Regulatory Sequences and Human Disease written by Nadav Ahituv and published by Springer Science & Business Media. This book was released on 2012-05-30 with total page 289 pages. Available in PDF, EPUB and Kindle. Book excerpt: In Gene Regulatory Sequences and Human Disease, the Editor will introduce the different technological advances that led to this breakthrough. In addition, several examples will be provided of nucleotide variants in noncoding sequences that have been shown to be associated with various human diseases.
Book Synopsis Epigenetics: Development and Disease by : Tapas Kumar Kundu
Download or read book Epigenetics: Development and Disease written by Tapas Kumar Kundu and published by Springer Science & Business Media. This book was released on 2012-11-13 with total page 698 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetics fine-tunes the life processes dictated by DNA sequences, but also kick-starts pathophysiological processes including diabetes, AIDS and cancer. This volume tracks the latest research on epigenetics, including work on new-generation therapeutics.
