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Author: Amelia Casamassimi
Publisher: MDPI
ISBN: 3039212656
Category : Science
Languages : en
Pages : 358
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Book Description
This book is a printed edition of the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation that was published in IJMS
Author: Amelia Casamassimi
Publisher: MDPI
ISBN: 3039212656
Category : Science
Languages : en
Pages : 358
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Book Description
This book is a printed edition of the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation that was published in IJMS
Author: Amelia Casamassimi
Publisher:
ISBN: 9783036577364
Category :
Languages : en
Pages : 0
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Book Description
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.
Author: Amelia Casamassimi
Publisher: Mdpi AG
ISBN: 9783036577371
Category : Science
Languages : en
Pages : 0
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Book Description
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.
Author: Albert J. Courey
Publisher: John Wiley & Sons
ISBN: 1444300458
Category : Science
Languages : en
Pages : 248
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Book Description
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
Author: Susanne Anke Kassube
Publisher:
ISBN:
Category :
Languages : en
Pages : 101
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Book Description
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.
Author: Robert O. J. Weinzierl
Publisher: World Scientific Publishing Company Incorporated
ISBN: 9781860941269
Category : Science
Languages : en
Pages : 424
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Book Description
"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
Author: Tsz-Leung To
Publisher:
ISBN:
Category :
Languages : en
Pages : 133
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Book Description
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.
Author: Carsten Carlberg
Publisher: Springer
ISBN: 9401777411
Category : Medical
Languages : en
Pages : 219
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Book Description
This textbook aims to describe the fascinating area of eukaryotic gene regulation for graduate students in all areas of the biomedical sciences. Gene expression is essential in shaping the various phenotypes of cells and tissues and as such, regulation of gene expression is a fundamental aspect of nearly all processes in physiology, both in healthy and in diseased states. This pivotal role for the regulation of gene expression makes this textbook essential reading for students of all the biomedical sciences, in order to be better prepared for their specialized disciplines. A complete understanding of transcription factors and the processes that alter their activity is a major goal of modern life science research. The availability of the whole human genome sequence (and that of other eukaryotic genomes) and the consequent development of next-generation sequencing technologies have significantly changed nearly all areas of the biological sciences. For example, the genome-wide location of histone modifications and transcription factor binding sites, such as provided by the ENCODE consortium, has greatly improved our understanding of gene regulation. Therefore, the focus of this book is the description of the post-genome understanding of gene regulation. The purpose of this book is to provide, in a condensed form, an overview on the present understanding of the mechanisms of gene regulation. The authors are not aiming to compete with comprehensive treatises, but rather focus on the essentials. Therefore, the authors have favored a high figure-to-text ratio following the rule stating that “a picture tells more than thousand words”. The content of the book is based on the lecture course, which is given by Prof. Carlberg since 2001 at the University of Eastern Finland in Kuopio. The book is subdivided into 4 sections and 13 chapters. Following the Introduction there are three sections, which take a view on gene regulation from the perspective of transcription factors, chromatin and non-coding RNA, respectively. Besides its value as a textbook, Mechanisms of Gene Regulation will be a useful reference for individuals working in biomedical laboratories.
Author: Brian L. Nelms
Publisher: Morgan & Claypool Publishers
ISBN: 161504048X
Category : Science
Languages : en
Pages : 227
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Book Description
The neural crest is a remarkable embryonic population of cells found only in vertebrates and has the potential to give rise to many different cell types contributing throughout the body. These derivatives range from the mesenchymal bone and cartilage comprising the facial skeleton, to neuronal derivatives of the peripheral sensory and autonomic nervous systems, to melanocytes throughout the body, and to smooth muscle of the great arteries of the heart. For these cells to correctly progress from an unspecifi ed, nonmigratory population to a wide array of dynamic, differentiated cell types-some of which retain stem cell characteristics presumably to replenish these derivatives-requires a complex network of molecular switches to control the gene programs giving these cells their defi ning structural, enzymatic, migratory, and signaling capacities. This review will bring together current knowledge of neural crest-specifi c transcription factors governing these progressions throughout the course of development. A more thorough understanding of the mechanisms of transcriptional control in differentiation will aid in strategies designed to push undifferentiated cells toward a particular lineage, and unraveling these processes will help toward reprogramming cells from a differentiated to a more naive state. Table of Contents: Introduction / AP Genes / bHLH Genes / ETS Genes / Fox Genes / Homeobox Genes / Hox Genes / Lim Genes / Pax Genes / POU Domain Genes / RAR/RXR Genes / Smad Genes / Sox Genes / Zinc Finger Genes / Other Miscellaneous Genes / References / Author Biographies
Author: Sam Thiagalingam
Publisher: Cambridge University Press
ISBN: 0521493390
Category : Mathematics
Languages : en
Pages : 597
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Book Description
An overview of the current systems biology-based knowledge and the experimental approaches for deciphering the biological basis of cancer.
