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Author: John C. Manteiga
Publisher:
ISBN:
Category :
Languages : en
Pages : 148
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Book Description
Gene regulation underlies the control of cell identity, development, and disease. Transcription of genes is regulated by DNA elements called enhancers, which are bound by transcription factors and coactivators, leading to the recruitment of RNA polymerase II and the production of RNA. Enhancers are thought to loop to specific gene promoters to stimulate transcription, but the mechanisms that cause enhancers to selectively loop to specific gene promoters is not well understood. In this thesis, I first describe new insights into enhancer-promoter loop specificity from studies examining the mechanisms that allow tumor-specific super-enhancers to loop to the MYC oncogene in diverse cancer types (Schuijers and Manteiga et al., 2018). While conducting these studies, it was proposed that super-enhancers and the factors associated with them form liquid-liquid phase-separated condensates. Following this proposal, I contributed to collaborative studies that strongly supported this model (Boija et al., 2018; Sabari et al., 2018, see Appendix I and II of this thesis). This model of transcription led me to ask how key transcriptional components could be recruited into super-enhancer condensates. I performed studies showing that the interaction of RNA polymerase II with these condensates involves the large heptapeptide repeat of the C-terminal domain (CTD) of the enzyme. Furthermore, these studies provided evidence that phosphorylation of the CTD, which is associated with the initiation to elongation transition, weakens these interactions, thus facilitating the transition of RNA polymerase II into different condensates involved in co-transcriptional splicing of the nascent transcript (Guo and Manteiga et al., 2019). These studies provide new insights into the mechanisms of enhancer-promoter interaction, roles for the RNA polymerase II CTD in the enzyme’s partitioning into nuclear condensates, and a role for phosphorylation in switching the nuclear condensate partitioning behavior of RNA polymerase II.
Author: John C. Manteiga
Publisher:
ISBN:
Category :
Languages : en
Pages : 148
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Book Description
Gene regulation underlies the control of cell identity, development, and disease. Transcription of genes is regulated by DNA elements called enhancers, which are bound by transcription factors and coactivators, leading to the recruitment of RNA polymerase II and the production of RNA. Enhancers are thought to loop to specific gene promoters to stimulate transcription, but the mechanisms that cause enhancers to selectively loop to specific gene promoters is not well understood. In this thesis, I first describe new insights into enhancer-promoter loop specificity from studies examining the mechanisms that allow tumor-specific super-enhancers to loop to the MYC oncogene in diverse cancer types (Schuijers and Manteiga et al., 2018). While conducting these studies, it was proposed that super-enhancers and the factors associated with them form liquid-liquid phase-separated condensates. Following this proposal, I contributed to collaborative studies that strongly supported this model (Boija et al., 2018; Sabari et al., 2018, see Appendix I and II of this thesis). This model of transcription led me to ask how key transcriptional components could be recruited into super-enhancer condensates. I performed studies showing that the interaction of RNA polymerase II with these condensates involves the large heptapeptide repeat of the C-terminal domain (CTD) of the enzyme. Furthermore, these studies provided evidence that phosphorylation of the CTD, which is associated with the initiation to elongation transition, weakens these interactions, thus facilitating the transition of RNA polymerase II into different condensates involved in co-transcriptional splicing of the nascent transcript (Guo and Manteiga et al., 2019). These studies provide new insights into the mechanisms of enhancer-promoter interaction, roles for the RNA polymerase II CTD in the enzyme’s partitioning into nuclear condensates, and a role for phosphorylation in switching the nuclear condensate partitioning behavior of RNA polymerase II.
Author: Krishna Shrinivas (Ph. D.)
Publisher:
ISBN:
Category :
Languages : en
Pages : 221
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Book Description
Human development and physiology depend on the coordinated function of thousands of cell types – for example, neurons, immune cells, and skin cells. Each cell-type contains an identical copy of the genetic material yet performs specialized and diverse functions, in large part, due to the selective expression of particular coding DNA-elements (genes) into RNA. Mutations or dysregulation in control of gene expression underlie many diseased states, including cancer and neurodegenerative disorders. Non-coding DNA elements called enhancers orchestrate the complex biochemical pathways that lead to precise activation of cell-type specific genes. Decades of advances in molecular biology have identified many of the key proteins and their interactions in these pathways. Yet, how dozens of proteins and their complex network of interactions are organized in space and time by enhancers to robustly relay regulatory information to their target genes remains one of the central puzzles of transcriptional control. In this thesis, I will leverage approaches from statistical physics, simulation, and informatics, in synergy with experimentalists, to gain mechanistic insights into gene control through the lens of biomolecular phase transitions. Proposal: I will introduce recent evidence that proteins and nucleic acids with certain features phase separate into two liquid phases, like oil from water, to compartmentalize cellular pathways. Employing a simple physical model, I will propose the phase separation of the transcriptional machinery explains established and recently observed puzzles underlying a class of enhancer elements called super-enhancers. Subsequently, I will describe studies performed in collaboration with the Young and Sharp labs that provide direct experimental evidence of transcriptional condensates model in vivo. Mechanism: I then will describe our efforts to identify the mechanisms contributing to the formation of transcriptional condensates. By combining molecular dynamics, informatics, and experimental assays, we identify specific features encoded in DNA that enable spatio-temporally localized formation of condensates. I will discuss implications on the origins of enhancer activity. Control: Here, we’ll combine non-equilibrium models of phase separation, coacervate chemistry, and imaging data in cells to explore the dynamic control of transcription through it eventual outcome i.e. ATP-dependent synthesis of RNA. We propose a dual-feedback mechanism in which low levels of RNA synthesis promote condensate formation and higher levels trigger dissolution. I will close by discussing the ramifications of our model on two enigmatic features of transcription – the pervasive synthesis and degradation of non-coding RNA and discrete and bursty dynamics of mRNA synthesis. I will conclude with a short summary and brief discussion on future work.
Author: Ludovic Berthier
Publisher: OUP Oxford
ISBN: 0191621307
Category : Science
Languages : en
Pages : 464
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Book Description
Most of the solid materials we use in everyday life, from plastics to cosmetic gels exist under a non-crystalline, amorphous form: they are glasses. Yet, we are still seeking a fundamental explanation as to what glasses really are and to why they form. In this book, we survey the most recent theoretical and experimental research dealing with glassy physics, from molecular to colloidal glasses and granular media. Leading experts in this field present broad and original perspectives on one of the deepest mysteries of condensed matter physics, with an emphasis on the key role played by heterogeneities in the dynamics of glassiness.
Author: Rodolphe Barrangou
Publisher: Springer Science & Business Media
ISBN: 364234657X
Category : Science
Languages : en
Pages : 300
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Book Description
CRISPR/Cas is a recently described defense system that protects bacteria and archaea against invasion by mobile genetic elements such as viruses and plasmids. A wide spectrum of distinct CRISPR/Cas systems has been identified in at least half of the available prokaryotic genomes. On-going structural and functional analyses have resulted in a far greater insight into the functions and possible applications of these systems, although many secrets remain to be discovered. In this book, experts summarize the state of the art in this exciting field.
Author:
Publisher: Elsevier
ISBN: 0080546161
Category : Science
Languages : en
Pages : 577
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Book Description
This volume covers all aspects of embryonic stem cell differentiation, including mouse embryonic stem cells, mouse embryonic germ cells, monkey and human embryonic stem cells, and gene discovery.* Early commitment steps and generation of chimeric mice* Differentiation to mesoderm derivatives* Gene discovery by manipulation of mouse embryonic stem cells
Author: Oldenburg Oldenburg Press
Publisher:
ISBN: 9781523764426
Category :
Languages : en
Pages : 40
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Book Description
HiC-Pro is an optimized and flexible pipeline for processing Hi-C data from raw reads to normalized contact maps. HiC-Pro maps reads, detects valid ligation products, performs quality controls and generates intra- and inter-chromosomal contact maps. It includes a fast implementation of the iterative correction method and is based on a memory-efficient data format for Hi-C contact maps. In addition, HiC-Pro can use phased genotype data to build allele-specific contact maps. We applied HiC-Pro to different Hi-C datasets, demonstrating its ability to easily process large data in a reasonable time. Source code and documentation are available at http://github.com/nservant/HiC-Pro.
Author: Mirjana Pavlovic
Publisher: Springer Science & Business Media
ISBN: 1461455057
Category : Technology & Engineering
Languages : en
Pages : 159
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Book Description
Stem cells are the building blocks for all other cells in an organism. The human body has about 200 different types of cells and any of those cells can be produced by a stem cell. This fact emphasizes the significance of stem cells in transplantational medicine, regenerative therapy and bioengineering. Whether embryonic or adult, these cells can be used for the successful treatment of a wide range of diseases that were not treatable before, such as osteogenesis imperfecta in children, different forms of leukemias, acute myocardial infarction, some neural damages and diseases, etc. Bioengineering, e.g. successful manipulation of these cells with multipotential capacity of differentiation toward appropriate patterns and precise quantity, are the prerequisites for successful outcome and treatment. By combining in vivo and in vitro techniques, it is now possible to manage the wide spectrum of tissue damages and organ diseases. Although the stem-cell therapy is not a response to all the questions, it provides more and more answers every day. Stem Cells and Tissue Engineering is a concise review on the functional, phenotypic, regenerative, transplantational and curative aspects of a stem cell’s entity. It is critical and encouraging at the same time, providing truthful and appropriate samples from the practice and research that can lead toward optimal use of this immense source of adjuvant and curative therapy in human pathology. Written by a clinician and a researcher, who are currently teaching what they are doing, it is recommended as a teaching tool along with an original textbook.
Author: B. D. Hames
Publisher: Oxford University Press, USA
ISBN:
Category : Music
Languages : en
Pages : 238
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Book Description
This book gives a co-ordinated review of our present knowledge of eukaryotic RNA synthesis.
Author: U Satyanarayana
Publisher: Elsevier Health Sciences
ISBN: 8131241831
Category : Medical
Languages : en
Pages : 25
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Book Description
Regulation of gene expression Regulation of gene expression
Author: Yakov Gluzman
Publisher:
ISBN:
Category : Science
Languages : en
Pages : 238
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Book Description
