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Chromatin Regulation And Dynamics

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Chromatin Regulation and Dynamics

Chromatin Regulation and Dynamics Book
Author : Anita Göndör
Publisher : Academic Press
Release : 2016-10-25
ISBN : 0128034025
Language : En, Es, Fr & De

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Book Description :

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

Investigating the Roles of Histone Residues Chaperones and Modifiers in Chromatin Regulation Chromatin Dynamics and DNA Excision Repair

Investigating the Roles of Histone Residues  Chaperones  and Modifiers in Chromatin Regulation  Chromatin Dynamics  and DNA Excision Repair Book
Author : Amelia J. Hodges
Publisher : Unknown
Release : 2017
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

In a eukaryotic cell, DNA is packaged into chromatin, a highly dynamic and highly regulated structure. Chromatin is composed of nucleosome subunits, comprised of an octamer of histone proteins wrapped by DNA. Histone proteins are highly conserved among species, and also show a high degree of post-translational modification. In this work, we sought to better understand the roles of histone residues, histone domains, and histone modification in chromatin regulation and dynamics using Saccharomyces cerevisiae as a model eukaryote. In part one of this dissertation, we examine key residues and domains of histone proteins and how they interact with the cellular environment. First, we determined the "sprocket" arginine residues that project into the minor groove of DNA as it wraps around the histone octamer are important for cell viability, histone occupancy, gene expression and DNA repair. Second, we determined the nucleosome acidic patch that forms a negatively charged surface in the solvent-exposed region of the nucleosome is important for histone occupancy and binding to the essential histone chaperone FACT. Third, we found the histone H2B repression (HBR) domain in the H2B N-terminal tail is important for FACT binding and DNA damage resistance. Collectively, these studies increase our understanding of how unique features in histone structure regulate chromatin structure and interactions. In part two of this dissertation, we examine the roles of essential chromatin-associated factors in response to DNA damage. During the DNA damage response, chromatin must be transiently remodeled in order for DNA repair to occur. However, the roles of specific chromatin factors in the DNA damage response are still being elucidated. We optimized the anchor-away method to conditionally deplete essential chromatin factors from the yeast cell nucleus, and discovered the NuA4 histone acetyltransferase complex plays an important role in DNA excision repair. These studies highlight the role of essential chromatin factors in repairing DNA lesions.

Chromatin

Chromatin Book
Author : Ralf Blossey
Publisher : CRC Press
Release : 2017-08-04
ISBN : 149872938X
Language : En, Es, Fr & De

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Book Description :

An invaluable resource for computational biologists and researchers from other fields seeking an introduction to the topic, Chromatin: Structure, Dynamics, Regulation offers comprehensive coverage of this dynamic interdisciplinary field, from the basics to the latest research. Computational methods from statistical physics and bioinformatics are detailed whenever possible without lengthy recourse to specialized techniques.

Plant Chromatin Dynamics

Plant Chromatin Dynamics Book
Author : Marian Bemer,Célia Baroux
Publisher : Humana Press
Release : 2017-10-20
ISBN : 9781493973170
Language : En, Es, Fr & De

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Book Description :

This volume provides a comprehensive collection of protocols that can be used to study plant chromatin structure and composition. Chapters divided into three sections detail the profiling of chromatin features in relation to epigenetic regulation, investigate the interaction between chromatin modifications and gene regulation, and explore the 3D spatial organization of the chromatin inside the nucleus. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Plant Chromatin Dynamics: Methods and Protocols aims to ensure successful results in the further study of this vital field.

Chromatin Dynamics and the Regulation of beta globin Gene Expression

Chromatin Dynamics and the Regulation of  beta  globin Gene Expression Book
Author : Marcus Govert Johannes Maria Wijgerde
Publisher : Unknown
Release : 1998
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download Chromatin Dynamics and the Regulation of beta globin Gene Expression book written by Marcus Govert Johannes Maria Wijgerde, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Chromatin Dynamics in Cellular Function

Chromatin Dynamics in Cellular Function Book
Author : Brehon Laurent
Publisher : Springer
Release : 2014-03-14
ISBN : 9783642070242
Language : En, Es, Fr & De

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Book Description :

This volume includes timely reviews of several aspects of chromatin biology written by scientists at the forefront of this rapidly moving field. Topics covered include the structure and function of protein modules within chromatin-remodeling proteins, newly characterized histone modifications (methylation, ubiquitylation) and their functional consequences, transcription and histone dynamics, roles of chromatin remodeling factors in DNA replication and repair, and current models of nucleosome-remodeling mechanisms.

MYC and MNT in Transcriptional Regulation and Chromatin Dynamics

MYC and MNT in Transcriptional Regulation and Chromatin Dynamics Book
Author : Anonim
Publisher : Unknown
Release : 2014
ISBN : 9789175493770
Language : En, Es, Fr & De

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Book Description :

Download MYC and MNT in Transcriptional Regulation and Chromatin Dynamics book written by , available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Characterization of Chromatin Dynamics During DNA Repair and Transcriptional Regulation

Characterization of Chromatin Dynamics During DNA Repair and Transcriptional Regulation Book
Author : Beth Ann Tamburini,University of Colorado at Denver and Health Sciences Center
Publisher : Unknown
Release : 2006
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download Characterization of Chromatin Dynamics During DNA Repair and Transcriptional Regulation book written by Beth Ann Tamburini,University of Colorado at Denver and Health Sciences Center, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

The Regulation of Chromatin Dynamics by Histone Chaperones and Variants

The Regulation of Chromatin Dynamics by Histone Chaperones and Variants Book
Author : Rachel Miriam Zunder
Publisher : Unknown
Release : 2011
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

In all eukaryotic organisms, DNA is packaged into chromatin, which controls gene expression and genomic stability. The chromatin landscape is dynamic and responds to environmental signals to direct different cellular programs. Chromatin architecture is regulated by a network of structural and enzymatic proteins that interact with histones to alter nucleosome composition. In my dissertation, I examined 1) the interaction between histone chaperones and newly synthesized histones during nucleosome assembly and 2) the interplay between canonical histone isotypes, histone variants, and histone modifications. My work established how the unusual domain architecture of a newly discovered histone chaperone, Rtt106, provides specificity for acetylated histone cargo. Additionally, I discovered several new histone modifications and examined the relationship between the histone variant H2A.Z and two canonical histone H2B isotypes (Htb1 and Htb2). My dissertation establishes a framework for understanding the additional levels of genomic regulation achieved by histone chaperones, variants, isotypes, and modifications. In chapter 2, I examine the structural basis for the specificity of the histone chaperone Rtt106 for H3 molecules modified by an acetylation at lysine 56 (H3K56ac). The X ray crystal structure, determined by our collaborators Andy Antczak and James Berger, revealed that Rtt106 contains a double pleckstrin homology (PH) motif. A targeted mutational screen identified two regions on Rtt106 that, when mutated individually, each disrupted Rtt106-H3 binding. One region was a basic surface on the N-terminal PH domain and the other was a loop within the C-terminal PH domain. Although binding experiments did not directly identify an H3K56ac binding pocket on Rtt106, a comparative analysis with the chromatin remodeling protein Pob3 implicated the C-terminal loop as the source of H3K56ac-specificity in the Rtt106-H3 interaction. This work establishes new domain architecture for acetyl-lysine recognition and expands our understanding of how chaperone-histone binding is regulated. Armed with Rtt106 mutants that reduced H3 binding activity, in chapter 3 I examine the role of Rtt106-mediated nucleosome assembly during replication, transcription, and silencing. Although Rtt106 mutant proteins localized to origins of replication and silent chromatin, without the ability to bind H3, these mutants could not deliver H3K56ac into chromatin. Reduced H3K56ac occupancy was detrimental to replication whereas excess unincorporated H3K56ac was antagonistic to silencing. In contrast, H3K56ac binding was required to recruit Rtt106 to histone gene promoters. Without recruitment of Rtt106 to these loci, we observed defects in H3K56ac incorporation and histone gene repression. Our work demonstrates that Rtt106-H3 binding is necessary for all known branches Rtt106-mediated nucleosome assembly, however these different branches rely on distinct genomic localization cues to target Rtt106 to chromatin. To analyze the relationships between canonical histones, modifications, and variants, in chapter 4 I explore the unique functions of two histone H2B isotypes, Htb1 and Htb2. In collaboration with the Freitas lab at the Ohio State University, we discovered three new modifications on H2B, one of which was isotype-specific. Although the dimeric association of H2A.Z with H2B did not reveal an isotype-specific interaction, the interplay between canonical histone isotypes and variants remains an intriguing paradigm for chromatin regulation. In collaboration with the Giaever lab at the University of Toronto, we used chemical genomic profiling to define unique functions associated with the Htb1 and Htb2 isotypes. However, all chemical sensitivities identified resulted from changes in histone expression rather than Htb1 and Htb2 protein activity. Although we are still searching for a functional distinction between the two H2B isotypes, mass spectrometry analyses coupled with chemical-genomic profiling represents a promising strategy for discovering these relationships and defining their functional impact.

MADS Dynamics

MADS Dynamics Book
Author : Anonim
Publisher : Unknown
Release : 2015
ISBN : 9789462572669
Language : En, Es, Fr & De

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Book Description :

Download MADS Dynamics book written by , available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

From DNA Sequence to Chromatin Dynamics

From DNA Sequence to Chromatin Dynamics Book
Author : Tommy Kaplan
Publisher : Unknown
Release : 2008
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download From DNA Sequence to Chromatin Dynamics book written by Tommy Kaplan, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Chromatin Structure and Dynamics

Chromatin Structure and Dynamics Book
Author : J. Zlatanova,S. H. Leuba
Publisher : Gulf Professional Publishing
Release : 2004
ISBN : 9780444515940
Language : En, Es, Fr & De

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Book Description :

Biological processes that replicate, preserve and use the genetic information encoded in DNA must operate in the context of chromatin, a highly organized complex of DNA and proteins. These proteins do not merely package the DNA in the tiny volume of the nucleus, but impart the structure the ability to change according to the requirements of the specific process the DNA is involved in. Moreover, chromatin structure is used by the cell to control the activity of DNA. In this volume the basics of chromatin structure and dynamics are presented by established experts in the field.

The Epigenetic Regulation of Cell Cycle and Chromatin Dynamic by Sirtuins

The Epigenetic Regulation of Cell Cycle and Chromatin Dynamic by Sirtuins Book
Author : Paloma Martínez Redondo,Esteban Ballestar Tarín,Universitat de Barcelona. Facultat de Farmàcia
Publisher : Unknown
Release : 2014
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

The chromatin consists of a hierarchical and dynamical structure that is modulated during the different cell cycle stages in order to maintain genome integrity and preserve the genetic information coded in the DNA. The dynamic structure of the chromatin depends on the coordination of the different chromatin remodeling processes: histone modifications, chromatin remodeling enzymes/complexes, DNA methylation and chromatin architectural proteins (CAPs). Within the chromatin, the histone-mediated regulation responds mainly to the modification of its N-terminal domain or "tail." Among the different histone modifications, acetylation at specific lysine residues (K) is one of the best characterized, and the acetylation of lysine 16 of histone H4 is the most frequently acetylated residue in eukaryotes. The acetylated form of H4K16 is an important mark of actively transcribed euchromatin from yeast to humans; whereas its non acetylated form is associated with gene silencing and heterochromatin regions. The dynamics of this histone modification is mainly governed by three enzymes: the histone acetyltransferases (HAT) MOF (males absent of the first), and the histone deacetylases (HDAC) SIRT1 and SIRT2. Therefore, both groups of enzymes are essential for the regulation of gene expression and chromatin organization in the nucleus, regulating the transition between transcriptionally active and inactive state of chromatin. SIRT1 and SIRT2 belong to the Class III of HDACs, termed as sirtuins, which are crucial for genomic integrity, adaptation to the environment and aging, among other functions. On one hand, SIRT2 is the only mammalian sirtuin located in the cytoplasm, which is known to shuttle to the nucleus during G2/M. Consistently, this HDAC has its main role in deacetylating H4K16Ac during G2-M. So far, the role of SIRT2 as the main H4K16Ac during mitosis has only been demonstrated by mammalian cell culture experiments or yeast studies. Therefore, for the first time, our study demonstrates the essential role of SIRT2 in regulating H4K16Ac levels during mitosis in vivo. As a matter of fact, our results support the function of SIRT2 in regulating chromatin dynamics by its involvement in the control not only of H4K16Ac levels, but also of H4K20me1-3 levels during the whole cell cycle. Notwithstanding, as happens with other sirtuin members, SIRT2 has also been shown to regulate and deacetylate non-histone substrates that govern cell cycle, stress response, cell survival and genome stability. Furthermore, one of the main roles of SIRT2 consists of modulating cell cycle progression and SIRT2 has been found to regulate diverse mitotic checkpoint proteins such as CDH1, CDC20, BubR1 and p53. Additionally, our results suggest that the chromatin histone patterns generated by SIRT2 during mitosis are essential in the control of cell cycle progression and attend to two complementary mechanisms: the deacetylation of both H4K16Ac and PR-Set7, the monomethyltrasferase of H4K20. We have found that SIRT2 is clearly involved in a mitotic checkpoint and regulate H4K20me1 deposition under stressful conditions, in order to preserve genome integrity. On the other hand, SIRT1 has been mainly involved in regulating heterochomatin formation and gene silencing by deacetylating histone and non-histone substrates. In fact, SIRT1 is involved in the maintenance of genome integrity due to its role in heterochromatin formation by deacetylating histone marks (H3K9Ac and H1K26Ac) and regulating heterochromatin related proteins such as HP1, Suv39h1 and Ezh2. In addition, SIRT1 also deacetylates H4K16Ac, H3K9Ac and H1K26Ac at specific promoters in order to control gene expression; and regulates non-histone proteins such as p53, FoxO factors, and Rb, among others, to specifically modulate the gene expression pattern. Nonetheless, SIRT1 has recently been implicated in cell cycle regulation throughout the control of Mcm10, the eukaryotic DNA initiation factor essential for S-phase progression. Accordingly, our study also demonstrate how SIRT1 may be involved in the regulation of cell cycle progression by modulating the expression of PR-Set7 and Suv4-20h2, the enzymes in charge of mono- and di-methylate H4K20, respectively. Altogether this evidences the role of sirtuins in preserving genome integrity by modulating chromatin dynamics and cell cycle progression from mitosis to S-phase.

Regulation of Nucleosome Dynamics

Regulation of Nucleosome Dynamics Book
Author : Justin Andrew North
Publisher : Unknown
Release : 2012
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Abstract: The DNA in eukaryotic cells is organized into a tightly-regulated structural polymer called chromatin that ultimately controls crucial functions of the genome, including gene expression, DNA synthesis, and repair. The basic unit of chromatin is the nucleosome in which 147 base pairs of DNA wraps 1.7-times around eight "core" histone proteins (two copies each of H2A, H2B, H3, H4). Repeats of this structural unit have been shown to fold into higher order structures, which play a central role in controlling DNA accessibility for transcription regulation. However, at the individual nucleosome level, DNA-histone interactions that wrap DNA into the nucleosome also control DNA accessibility. A significant number of factors have been shown to regulate nucleosome accessibility, including variants and post-translational chemical modifications of to the core histone proteins, chromatin remodeling complexes that reposition and disassemble nucleosomes, and histone chaperones that deposit or remove histones. Ultimately, these chromatin regulatory factors must physically alter nucleosomes to change DNA accessibility to transcription, replication, and DNA repair machinery.

Nuclear Architecture and Dynamics

Nuclear Architecture and Dynamics Book
Author : Christophe Lavelle,Jean-Marc Victor
Publisher : Academic Press
Release : 2017-10-27
ISBN : 012803503X
Language : En, Es, Fr & De

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Book Description :

Nuclear Architecture and Dynamics provides a definitive resource for (bio)physicists and molecular and cellular biologists whose research involves an understanding of the organization of the genome and the mechanisms of its proper reading, maintenance, and replication by the cell. This book brings together the biochemical and physical characteristics of genome organization, providing a relevant framework in which to interpret the control of gene expression and cell differentiation. It includes work from a group of international experts, including biologists, physicists, mathematicians, and bioinformaticians who have come together for a comprehensive presentation of the current developments in the nuclear dynamics and architecture field. The book provides the uninitiated with an entry point to a highly dynamic, but complex issue, and the expert with an opportunity to have a fresh look at the viewpoints advocated by researchers from different disciplines. Highlights the link between the (bio)chemistry and the (bio)physics of chromatin Deciphers the complex interplay between numerous biochemical factors at task in the nucleus and the physical state of chromatin Provides a collective view of the field by a large, diverse group of authors with both physics and biology backgrounds

Characterization of Lysine Methylation in Epigenetic Regulation

Characterization of Lysine Methylation in Epigenetic Regulation Book
Author : Anonim
Publisher : Stanford University
Release : 2011
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Chromatin is the physiological template for all DNA processing events in eukaryotic cells. Dynamic regulation of chromatin between open and silent states determines the accessibility of underlying DNA to transcription factors or other effector proteins and hence influences biological processes epigenetically without alterations of DNA sequences. The dynamics of chromatin structure regulates diverse cellular functions, and the disruption of chromatin homeostasis is thought to fundamentally impact on the development and progression of cancers and other human diseases. One principal mechanism for regulating chromatin structure involves the reversible covalent post-translational modification of histone proteins by chemical moieties such as acetyl-, methyl- and phospho- groups. In recent years, emerging evidence has suggested a key role of lysine methylation in the regulation of dynamic chromatin structure. Various histone methyl marks orchestrate proper programming of the genome, and aberrant methylation signaling is implicated in the initiation and the progression of various types of cancers. In this article, we described the development of a novel microarray-based high-throughput methodology, human epigenome microarray platform (HEMP), to discover rapidly and accurately methyl lysine-sensitive readers. A number of proteome-wide studies were performed utilizing HEMP as screening approach, and many novel interactions were identified since the establishment of this powerful technology. Utilizing HEMP as screening approach, we identified that the non-canonical Plant Homeodomain (PHD) finger of recombination activating gene 2 (RAG2) specifically recognizes histone H3 tri-methylated at lysine 4 (H3K4me3), revealing for the first time the molecular link between histone methylation and V(D)J recombination. In addition, this article described the characterization of a protein lysine methyltransferase, NSD2, demonstrating the molecular mechanisms by which overexpression of NSD2 contributes to multiple myeloma pathogenesis. This study established biological and pathologic modes of action for NSD2 and presented a novel mechanism by which disruption of chromatin homeostasis contributes to cancer.

Developing Computational and Experimental Tools to Understand Chromatin Dynamics and Regulation

Developing Computational and Experimental Tools to Understand Chromatin Dynamics and Regulation Book
Author : Linfeng Yang
Publisher : Unknown
Release : 2020
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

The human genome is condensed yet accessible, allowing cells to execute complex logic needed for cellular programs. The dynamic physical organization of the genome is connected to its instantaneous transcriptional profile. Current sequencing technologies can only recover a static and highly-averaged picture of these dynamic processes. Identification of dynamic signatures from chromatin motion requires an imaging and analysis platform for simultaneous tracking of genes and their transcriptional state in live cells. Advances in microscopy have provided a great opportunity to obtain such information. Unfortunately, segmenting overlapping nuclei is still a major challenge for single cell microscopic measurement. We first reported a deep-learning based model 'Nuclear Segmentation Tool' (NuSeT) that accurately segments multiple types of nuclei from imaging data. Using a hybrid architecture that consists of U-Net and Region Proposal Networks (RPN), followed by watershed processing, NuSeT has achieved superior performance in delineating nuclear boundaries in images of varying complexities. NuSeT further improves nuclear detection and reduces false positives by employing foreground normalization and additional training on synthetic images containing non-cellular artifacts. NuSeT also addresses common bottlenecks in nuclear segmentation such as limited training samples, variability in nuclear signal and shapes, and sample preparation artifacts. NuSeT consistently fares better in generating accurate segmentation masks and assigning boundaries for touching nuclei compared with other state-of-the-art segmentation models. Next, we developed an imaging platform for simultaneous real-time visualization of locus dynamics and transcriptional output. Using a CRISPR/Cas9 based gene knock-in strategy, we have introduced MS2 hairpin cassettes into native genes of interest, which can reveal their transcriptional states. To track these loci for extended periods of time at high spatiotemporal resolution, we have generated optical tag ArrayG/N fusions of the nuclease deactivated Cas9 (dCas9) and a polycistronic cassette of repeating tRNA-sgRNA delivered by lentivirus. This platform enables sustainable tracking of non-repetitive genomic loci. We have further modified ArrayG/N tags to recruit chromatin effectors at selected genomic sites that makes this experimental platform particularly well suited for dynamic monitoring of epigenetic manipulations on selected genes. Using this platform, we have measured dynamic signatures of chromatin accessibility. We have also shown that the motion of gene loci are further constrained when they are transcriptionally active. These image analysis and cellular engineering tools can be used to answer other outstanding questions about the chromatin and gene regulation dynamics.

Using Chromatin Dynamics to Understand Transcriptional Regulation and Genetic Variance

Using Chromatin Dynamics to Understand Transcriptional Regulation and Genetic Variance Book
Author : Samantha Nicole Piekos
Publisher : Unknown
Release : 2020
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

The genome is the same in every cell of an organism, but complex organisms have multiple cell types. This is due to the epigenome specifying a cell's transcriptional state resulting in distinct cell identities. Despite 98.5% of the human genome is non-coding and the site of epigenomic activity, which specifies instructions for regulating transcription of the coding region, relatively little is known about its function. A major hurdle with studying non-coding regulatory elements is identifying their distal gene and regulatory targets. Here, I solve this issue by using the three-dimensional chromatin conformation to identify targets that are in close physical proximity of the regulatory element. By integrating data on the three-dimensional chromatin state with other epigenomic measures including the open chromatin regions, transcription factor binding sites, and histone modifications I provide genome-wide insight into how the epigenome establishes the transcriptional state of the cell. In addition, I have developed a new method for prioritizing non-coding genetic variants in complex phenotypes. I validated this method in the context of Type 1 Diabetes and craniofacial disorders. In this dissertation, I demonstrate how data integration of multiple measurements of the epigenome and transcriptome provides insight into methods of transcriptional regulation and how this regulation is influenced by genetic variance.

Mapping and Dynamics of Regulatory DNA and Transcription Factor Networks in A Thaliana

Mapping and Dynamics of Regulatory DNA and Transcription Factor Networks in A  Thaliana Book
Author : Alessandra Maria Sullivan
Publisher : Unknown
Release : 2014
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Our understanding of gene regulation in plants is constrained by our limited knowledge of plant cis-regulatory DNA and its dynamics. One way in which cis-regulatory elements can be delineated is by their characteristic hypersensitivity to the endonuclease DNase I. In this dissertation I present the development and application of a DNase I-based assay for A. thaliana. I describe the development of a DNase I-seq method that can be used to map genome-wide chromatin accessibility with nucleotide resolution and cell-type specificity. I then use this method to map DNase I hypersensitive sites (DHSs) in A. thaliana seedlings and use genomic footprinting to delineate ~700,000 sites of in vivo transcription factor (TF) occupancy. I reveal general properties of DHSs in A. thaliana are novel, including evidence that highly significant GWAS variants are enriched within DHSs and that widespread TF binding within exons may have shaped codon usage patterns. I also show that the architecture of A. thaliana TF regulatory networks is strikingly similar to that of animals in spite of diverged regulatory repertoires. I then explore chromatin dynamics in response to environmental stimuli by mapping the chromatin landscape during heat shock and photomorphogenesis, disclosing thousands of environmentally-sensitive elements and the TFs that bind them. Next, I continue exploring chromatin dynamics, this time looking at developmentally dynamic DHSs during the maturation of seed-coat epidermal cells during the transition from growth to mucilage secretion. I show that differentially expressed genes are associated with dynamic DHSs and implicate new TFs and candidate genes involved in seed coat epidermal differentiation. Finally, I investigate the natural variation in chromatin accessibility through the examination of chromatin landscapes of 5 diverse A. thaliana ecotypes. I show that variable DHSs are more polymorphic than static DHSs across the accessions. I also show that deletions account for 15% of variable DHSs, suggesting they are a powerful force in shaping diverse patterns of gene regulation in the ecotypes. In the appendices I present supplemental figures and methods for Chapter 2, as well as a project summary and general information on phenotypic robustness, which is affected by cis-regulatory elements.