Transcriptional Regulation Molecules Involved Mechanisms And Misregulation
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Transcriptional Regulation Molecules Involved Mechanisms And Misregulation
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Author : Amelia Casamassimi
language : en
Publisher: MDPI
Release Date : 2019-07-30
Transcriptional Regulation Molecules Involved Mechanisms And Misregulation written by Amelia Casamassimi and has been published by MDPI this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-07-30 with Science categories.
This book is a printed edition of the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation that was published in IJMS
Transcriptional Regulation And Its Misregulation In Human Diseases
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Author : Amelia Casamassimi
language : en
Publisher:
Release Date : 2023
Transcriptional Regulation And Its Misregulation In Human Diseases written by Amelia Casamassimi and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2023 with categories.
Transcriptional regulation is a critical biological process that allows the cell or an organism to respond to a variety of intra- and extracellular signals, to define cell identity during development, to maintain it throughout its lifetime, and to coordinate cellular activity. This control involves multiple temporal and functional steps as well as innumerable molecules including transcription factors, cofactors, and chromatin regulators. It is well known that many human disorders are characterized by global transcriptional dysregulation because most of the signaling pathways ultimately target transcription machinery. Indeed, many syndromes and genetic and complex diseases--cancer, autoimmunity, neurological and developmental disorders, and metabolic and cardiovascular diseases--can be caused by mutations/alterations in regulatory sequences, transcription factors, splicing regulators, cofactors, chromatin regulators, ncRNAs, and other components of transcription apparatus. It is worth noting that advances in our understanding of molecules and mechanisms involved in the transcriptional circuitry and apparatus lead to new insights into the pathogenetic mechanisms of various human diseases and disorders. Thus, this Special Issue is focused on molecular genetics and genomics studies exploring the effects of transcriptional misregulation on human diseases.
Transcriptional Regulation And Its Misregulation In Human Diseases
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Author : Amelia Casamassimi
language : en
Publisher: Mdpi AG
Release Date : 2023-05-24
Transcriptional Regulation And Its Misregulation In Human Diseases written by Amelia Casamassimi and has been published by Mdpi AG this book supported file pdf, txt, epub, kindle and other format this book has been release on 2023-05-24 with Science categories.
Transcriptional regulation is a critical biological process that allows the cell or an organism to respond to a variety of intra- and extracellular signals, to define cell identity during development, to maintain it throughout its lifetime, and to coordinate cellular activity. This control involves multiple temporal and functional steps as well as innumerable molecules including transcription factors, cofactors, and chromatin regulators. It is well known that many human disorders are characterized by global transcriptional dysregulation because most of the signaling pathways ultimately target transcription machinery. Indeed, many syndromes and genetic and complex diseases-cancer, autoimmunity, neurological and developmental disorders, and metabolic and cardiovascular diseases-can be caused by mutations/alterations in regulatory sequences, transcription factors, splicing regulators, cofactors, chromatin regulators, ncRNAs, and other components of transcription apparatus. It is worth noting that advances in our understanding of molecules and mechanisms involved in the transcriptional circuitry and apparatus lead to new insights into the pathogenetic mechanisms of various human diseases and disorders. Thus, this Special Issue is focused on molecular genetics and genomics studies exploring the effects of transcriptional misregulation on human diseases.
Molecular Mechanisms Of Transcription Regulation By Non Coding Rnas And The Dna Helicase Recql5
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Author : Susanne Anke Kassube
language : en
Publisher:
Release Date : 2013
Molecular Mechanisms Of Transcription Regulation By Non Coding Rnas And The Dna Helicase Recql5 written by Susanne Anke Kassube and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013 with categories.
Transcription is the process of copying a fragment of DNA in the cell's nucleus into RNA. This copy is then used as a template to produce proteins, or it functions by itself as an enzyme, structural element or regulator. Transcription of protein-coding genes in eukaryotes is achieved by RNA polymerase II (Pol II), an enzyme that is tightly regulated to allow for the adaptation of transcript levels to both extracellular conditions as well as intracellular needs. My research has focused on understanding transcriptional regulation by two distinct factors: non-coding RNAs (ncRNAs) that are upregulated in response to cellular stress, and the DNA helicase RECQL5, a member of the highly conserved family of RecQ helicases involved in DNA repair. Non-coding RNAs are an important transcriptional regulator when cells adapt to extreme conditions such as heat shock. In mouse and human cells, heat shock triggers an increase in levels of B2/B1 RNA and Alu RNAs, respectively, which regulate expression of protein-coding genes by Pol II. Although it had been shown that ncRNAs interact directly with Pol II to regulate transcription, many important questions remained unanswered: Where is the binding site for ncRNAs located? Does binding of ncRNAs interfere with the binding of DNA to Pol II? How are repressive and non-repressive ncRNAs, which are both upregulated in response to heat shock and which both bind to Pol II with high affinity, distinguished? To address these questions, I employed single-particle cryo-electron microscopy (cryo-EM) to determine the structures of human Pol II in complex with six different repressive and non-repressive ncRNAs from mouse and human. The structural data allowed me to identify a conserved docking site for ncRNAs in the active site cleft of Pol II; the location of this site was later confirmed independently by cross-linking studies in collaboration with the laboratory of James Goodrich. Collectively, my analysis of the cryo-EM reconstructions of ncRNA-Pol II complexes in conjunction with biochemical data from the Goodrich lab suggest that the distinction between repressive and non-repressive ncRNAs is made by the general transcription factor TFIIF based on certain flexible RNA elements that extend beyond the docking site. RECQL5 is a DNA helicase implicated to function at the interface of the cellular DNA replication, DNA repair, and RNA transcription machineries. Although RECQL5 had previously been shown to interact directly with Pol II, its molecular mechanism of action remained elusive. My work aimed to answer the following questions: Where is the binding site for RECQL5 located on the surface of Pol II? Does binding of RECQL5 interfere with the binding of DNA or other transcription factors during transcription initiation or elongation? How is transcriptional repression by RECQL5 achieved at the molecular level? To answer these questions, we employed an integrative experimental approach, combining biochemical assays, X-ray crystallography, cryo-EM and small angle X-ray scattering. The crystal structure of a fragment of RECQL5's Pol II binding domain suggested that the topology of this domain is similar to a domain found in the transcription elongation factor TFIIS, which promotes continued transcription of arrested elongation complexes by stimulating the intrinsic RNA cleavage activity of Pol II. Using pull-down assays, I showed that RECQL5 and TFIIS compete for binding to Pol II, suggesting that the two proteins bind to overlapping sites. I corroborated these initial findings using an in vitro transcription assay, which confirmed that binding of RECQL5 to Pol II interferes with the function of TFIIS to promote read-through of intrinsic blocks to elongation. Using cryo-EM, I obtained a high-resolution reconstruction of an elongating Pol II complex repressed by RECQL5. By docking the known crystal structures of individual components into the EM map, I generated a pseudo-atomic model of the complex. This model confirmed the location of the binding site, and suggests a novel, dual mechanism for the regulation of transcription by RECQL5 that includes structural mimicry of the Pol II-TFIIS interaction. Both ncRNAs and RECQL5 are important regulatory factors in human cells whose molecular mechanisms of transcriptional repression remained unknown. My research has provided important insights into their structure and function and, in the case of RECQL5, uncovered a novel mechanism of transcription regulation that might be employed by a number of other factors involved in transcriptional repression at the interface of the DNA recombination, replication and repair machineries.
Mechanisms In Transcriptional Regulation
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Author : Albert J. Courey
language : en
Publisher: John Wiley & Sons
Release Date : 2009-01-22
Mechanisms In Transcriptional Regulation written by Albert J. Courey and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2009-01-22 with Science categories.
Mechanisms in Transcriptional Regulation provides a concisediscussion of the fundamental concepts in transcription and itsregulation. Covers RNA polymerases, transcriptional machinery, mechanismsof transcriptional activation, the histone code hypothesis, theepigenetic control of transcription, and combinatorial control insignaling and development Features over 80 figures available to download online Chapters include comprehensive reading lists, boxeshighlighting theoretical concepts and experimental methods andproblems designed to build and test understanding
Mechanisms Of Gene Expression
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Author : Robert O. J. Weinzierl
language : en
Publisher: World Scientific Publishing Company Incorporated
Release Date : 1999
Mechanisms Of Gene Expression written by Robert O. J. Weinzierl and has been published by World Scientific Publishing Company Incorporated this book supported file pdf, txt, epub, kindle and other format this book has been release on 1999 with Science categories.
"This book presents much of the current thinking concerning molecular mechanisms of transcriptional control in a form easily accessible to undergraduates with an understanding of basic molecular biology concepts. It contains detailed information about the various pro- and eukaryotic transcriptional machineries that has recently become available through the combined efforts of geneticists, biochemists and structural biologists. The book will thus not only serve as an undergraduate text but also offer something new and interesting to more advanced readers and professional scientists who want to keep up to date with rapid advances in this field."--BOOK JACKET.Title Summary field provided by Blackwell North America, Inc. All Rights Reserved
Transcription Factors
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Author : Paul J. Higgins
language : en
Publisher: Humana Press
Release Date : 2010-08-20
Transcription Factors written by Paul J. Higgins and has been published by Humana Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010-08-20 with Science categories.
In the last few years, significant breakthroughs in transcription research expanded our appreciation for the complexity of molecular controls on gene expression in mammalian cells. In Transcription Factors: Methods and Protocols, experts in the field describe state-of-the-art approaches that investigators can use to probe critical mechanisms underlying transcription factor nuclear-cytoplasmic trafficking as well as to assess the functional impact of post-translational modifications on transcription factor function. The chapters are written by prominent scientists, many of whom developed these methods, and highlight protocols that focus on specific transcription factor family members with particular relevance to human disease. Composed in the highly successful Methods in Molecular BiologyTM series format, each chapter contains a brief introduction, step-by-step methods, a list of necessary materials, and a Notes section which shares tips on troubleshooting and avoiding known pitfalls. Comprehensive and current, Transcription Factors: Methods and Protocols compiles the latest techniques for elucidating controls on transcription factor intracellular localization and activity, and consequently is unlike any other methods-based text on transcriptional regulation today.
Molecular Mechanisms Involved In Transcription Regulation Of Protein Encoding Genes
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Author : Wuchao Yuan
language : en
Publisher:
Release Date : 1996
Molecular Mechanisms Involved In Transcription Regulation Of Protein Encoding Genes written by Wuchao Yuan and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1996 with Molecular biology categories.
Regulatory Mechanisms Of Transcription And Associated Dna Repair
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Author : Shivani Malik
language : en
Publisher:
Release Date : 2012
Regulatory Mechanisms Of Transcription And Associated Dna Repair written by Shivani Malik and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012 with categories.
Transcription is a crucial regulatory step in gene regulation modulated by several proteins. Any misregulation during transcription can lead to many diseases including cancer, neurodegenerative disorders and aging making it imperative to have a detailed mechanistic view of the process. Over the recent years, 26S proteasome has been implicated in transcriptional regulation through its proteolytic and non-proteolytic activities. While, the proteolytic role of proteasome in transcription has been extensively studied, its non-proteolytic function is poorly understood. Thus, this thesis aims to analyze the non-proteolytic role of proteasome in transcription. The results have revealed the non-proteolytic role of 26S proteasome in establishing a specific protein interaction network at the promoter for stimulated transcriptional initiation in vivo. In addition to its roles in transcription, 26S proteasome also plays an important role in the degradation of RNA polymerase II stalled at DNA lesion facilitating the rapid repair of transcriptionally active genes through a process of transcription coupled repair (TCR). The author's studies have addressed the key question of the fate of RNA polymerase II stalled at a lesion. These findings show that RNA polymerase II interacts with an elongation and TCR-specific factor, Rad26p. Upon encountering a lesion, RNA polymerase II stalls and unloads Rad26p on the site of DNA damage. Subsequently, the elongating RNA polymerase II is disassembled through the degradation of its largest subunit, Rpb1p. Further; these studies have also uncovered a novel role of Rad26p in chromatin disassembly, which facilitates transcriptional elongation and hence TCR. This work provides valuable insights into interplay of chromatin structure, transcriptional elongation and TCR. Finally, extending the regulatory knowledge of sense transcriptional initiation to antisense, the author's work has revealed the extensive participation of GTFs in the process. Collectively, results of above studies provide a comprehensive view of transcription and associated process of active genome repair.
Transcriptional Bursting In Eukaryotic Gene Regulation
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Author : Tsz-Leung To
language : en
Publisher:
Release Date : 2010
Transcriptional Bursting In Eukaryotic Gene Regulation written by Tsz-Leung To and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with categories.
Transcription of mRNA appears to occur in random, intermittent bursts in a large variety of organisms. The statistics of mRNA expression can be described by two parameters: the frequency at which bursts occur (burst frequency) and the average number of mRNA produced within each burst (burst size). The mean steady-state abundance of mRNA is the product of the burst size and burst frequency. Although the experimental evidence for bursty gene transcription is abundant, little is known about its origins and consequences. We utilize single-molecule mRNA imaging and simple stochastic kinetic models to probe and understand both the mechanistic details and functional responses of transcriptional bursting in budding yeast. At the molecular level, we show that gene-specific activators can control both burst size and burst frequency by differentially utilizing kinetically distinct promoter elements. We also recognize the importance of activator residence time and nucleosome positioning on bursting. This investigation exemplifies how we can exploit spontaneous fluctuations in gene expression to uncover the molecular mechanisms and kinetic pathways of transcriptional regulation. At the network level, we demonstrate the important phenotypic consequences of transcriptional bursting by showing how noise itself can generate a bimodal, all-or-none gene expression profile that switches spontaneously between the low and high expression states in a transcriptional positive-feedback loop. Such bimodality is a hallmark in decision-making circuitry within metabolic, developmental, and synthetic gene regulatory networks. Importantly, we prove that the bimodal responses observed in our system are not due to deterministic bistability, which is an often-stated necessary condition for allor- none responses in positive-feedback loops. By clarifying a common misconception, this investigation provides unique biological insights into the molecular components, pathways and mechanisms controlling a measured phenotype.