Long-Range Control of Gene Expression

Long-Range Control of Gene Expression
Author: Veronica van Heyningen
Publisher: Academic Press
Total Pages: 415
Release: 2011-09-02
Genre: Science
ISBN: 0080877818

Long-Range Control of Gene Expression covers the current progress in understanding the mechanisms for genomic control of gene expression, which has grown considerably in the last few years as insight into genome organization and chromatin regulation has advanced. Discusses the evolution of cis-regulatory sequences in drosophila Includes information on genomic imprinting and imprinting defects in humans Includes a chapter on epigenetic gene regulation in cancer

Bridging Chromatin Architecture to Gene Expression

Bridging Chromatin Architecture to Gene Expression
Author: Jennifer Crutchley
Publisher:
Total Pages:
Release: 2015
Genre:
ISBN:

"There has been a great influx of information regarding the structures that our genome is packaged into, but how this occurs and how it relates to gene expression remains a mystery. Recently, Hi-C technology has revealed that our genome is organized in topological associated domains (TADs) and that at the boundaries of these TADs there is an increase of the previously characterized chromatin organization mediators, CTCF and cohesin. It is my objective to identify the role of CTCF and cohesin in the regulation of the gene expression and TAD boundary maintenance of the HOXA cluster. By employing siRNA and shRNA methodology in combination of 5C-seq technology, I identified that cohesin is the key mediator involved in maintaining the TAD boundary within the HOXA locus. Furthermore, loss of the cohesin complex resulted in an up-regulation of the 5'end HOXA genes, suggesting that the maintenance boundary is required to shut down the expression of the genes within that region. The results suggest that cohesin is the key mediator involved in the regulation and higher order chromatin structure of the HOXA cluster." --

Nuclear Organization, Chromatin Structure, and Gene Expression

Nuclear Organization, Chromatin Structure, and Gene Expression
Author: Roeland van Driel
Publisher: Oxford University Press on Demand
Total Pages: 295
Release: 1997
Genre: Science
ISBN: 9780198549239

This is one of the first books that focuses on emerging concepts about the role of the structure of chromatin, the organization of the genome, and the structure of the interphase nucleus in the control of gene expression in eukaryotes. The first section analyses the relationship between thedynamic chromatin structure at the nucleosome level and gene expression. Section two looks into higher order chromatin structure in relation to transcription. In section three the molecular basis of epigenetic phenomena, like X-chromosome inactivation is discussed, starting from our understanding ofchromatin structure. Together, these topics form the molecular basis for our understanding of cell differentiation, knowledge that is essential for the design of transgenic animals and plants and for gene therapy in humans. The book is of direct interest to students that are new in the field and toinvestigators in the area of biomolecular sciences, like developmental biology, biochemistry, cell biology, microbiology and genetics. Also, those working in applied fields of research, i.e biotechnology and biomedicine, will strongly benefit from this book. It will help them to understandfundamental problems in transgenics and gene therapy. Importantly, a variety of human disorders may turn out to be caused by genetic or somatic errors related to this level of gene control.

Chromatin Structure-Mediated Regulation of Nuclear Processes

Chromatin Structure-Mediated Regulation of Nuclear Processes
Author: Min Kim
Publisher:
Total Pages: 99
Release: 2013
Genre:
ISBN:

Chromatin is a mixture of DNA and DNA binding proteins that control transcription. Dynamic chromatin structure modulates gene expression and is responsible for an extraordinary spectrum of developmental processes. An intricate interplay of DNA methylation, histone modifications, histone variants, small RNA accumulation, and ATPase chromatin remodelers defines chromatin re-configuration in a precise manner, locally within a cell and globally across different cell types. The development of high-throughput screening methods such as microarray and whole-genome sequencing has led to an explosion of chromatin studies in the past decade. Moreover, genetic and molecular studies resulted in identification of a number of proteins that may influence chromatin structure. However, the exact functions of individual proteins as well as their functional relationships to each other are less understood. Also, the role of chromatin components in establishing cell- and tissue-specific chromatin structure is largely unknown. To address these open questions in chromatin biology, I focused my dissertation work on 1) studying tissue-specific DNA demethylation in seed, and 2) determining the role of a ubiquitous DNA binding protein, linker histone H1, in regulating chromatin structure. Tissue specific DNA methylation in seed. In endosperm, the nutritive tissue that nourishes the embryo, parent-of-origin specific gene expression is regulated by DNA demethylation. However, the extent to which DNA demethylation occurs in a tissue-specific manner and regulates transcription in the endosperm of crop plants like rice remains unknown. To address these questions, my colleagues and I examined the DNA methylation patterns of two rice seed tissues, embryo and endosperm. We found that endosperm genome is globally hypomethylated at non-CG sites and locally hypomethylated at CG-sites compared to embryo. We also identified that small transposons near genes (euchromatic regions) are the primary targets of DNA demethylation. The loci near the genes preferentially expressed in endosperm (e.g. storage protein and starch synthesizing enzymes) are subjected to local hypomethylation, suggesting that DNA methylation plays a role in inducing tissue-specific genes in endosperm. The role of H1 in regulating chromatin structure. H1 is proposed to facilitate higher order chromatin structure, but its effects on individual chromatin components and transcription are less understood. To resolve this issue, we investigated the role of H1 in regulating DNA methylation, nucleosome positioning, and transcription. We identified that H1 was most enriched in transposons. H1 was also found in genes at a lower level compared to transposons, and the abundance of H1 was anticorrelated with gene expression. Moreover, H1 influences nucleosome positioning by increasing the distance between two nucleosomes. Lack of H1 resulted in increased DNA methylation of transposons with heterochromatic features. In contrast, an h1 mutant showed a reduction of DNA methylation in genes and transposons with euchromatic features. Our finding suggests that H1 has a dual function in regulating DNA methylation. That is, H1 inhibits both DNA methyltransferases and DNA demethylation-associated enzymes from binding heterochromatin and euchromatin, respectively. In addition, the hypermethylated loci in our h1 mutant almost perfectly overlapped with the hypomethylated loci in a ddm1 mutant in heterochromatin, suggesting a link between these two proteins. DDM1 is an Snf2 chromatin remodeler that can slide nucleosomes along DNA and has been proposed to provide DNA methyltransferase access to target sequences. We further determined their functional relationship by crossing h1 and ddm1 mutants, and generated a map of DNA methylation of the cross. We identified that loss of DNA methylation from ddm1 was partially recovered by removing H1. Also the mutant phenotype observed in ddm1 disappeared in h1ddm1. Based on our results, we proposed a model where DDM1-mediated chromatin destabilization releases H1 binding, which in turn increases DNA accessibility. It is noteworthy that DNA demethylation preferentially occurred in euchromatin in both the rice seed DNA methylation study and the H1 study. Based on this result, we proposed that the apparent target preference of DNA demethylation-associated proteins depends on the underlying chromatin structure. We think that this chromatin structure-mediated specificity also dictates other nucleoproteins to determine/recognize their targets. My dissertation work tackled multiple aspects of chromatin biology: tissue-specific chromatin regulation, and the interplay between chromatin components in chromatin organization. Together, the results from my work enhanced our knowledge of how chromatin components influence overall chromatin structure.

Higher Order Chromatin Architecture in Mammalian Genomes

Higher Order Chromatin Architecture in Mammalian Genomes
Author: Jesse Raymond Dixon
Publisher:
Total Pages: 177
Release: 2013
Genre:
ISBN: 9781303197864

A detailed understanding of higher order chromatin structure is critical to understand the mechanisms used by regulatory elements to affect expression of their target genes. Yet, until recently, most methods used to study higher order chromatin structure were laborious and low-throughput. Recent advancements in the methods used to study chromatin structure have allowed for the first time the identification of genome wide patterns of higher-order chromatin interactions. During my Ph.D, I have used the Hi-C technique to study genome wide patterns of chromatin interactions. I have observed that chromosomes appear to fold into megabase-sized self-interacting structures that we have termed "topological domains." These domains are stable between cell types and conserved in evolution. These domains appear to be separated from each other by boundary elements in the genome, and appear to contain clusters of co-regulated cis-acting elements. The structure of the domains is dependent on the DNA-binding factor CTCF and the Cohesin complex. Notably, Cohesin and CTCF appear to have unique roles in regulating domain structure. CTCF appears to affect both intra- and inter-domain interactions, whereas Cohesin appears to primarily affect intra-domain interactions. When we compare topological domain interaction patterns across a variety of embryonic stem cell derived lineages, we observe that the interactions appear to be regulated on a domain-wide scale. Increases in domain-wide interaction frequency within domains correlates with active histone modifications, DNaseI hypersensitivity, and increased gene expression. In addition, we observe a wide-spread re-organization of inter-domain interactions between cell types. This correlates with a re-structuring of the "A" and "B" compartments in the nucleus. The alterations of the A/B compartments appear to modestly correlate with changes in gene expression, most notably for particular subsets of genes. We anticipate that these studies will lay the ground work for future experiments to elucidate the impact of higher order chromatin structures on diverse fields of biology, ranging from human disease to the evolution of genomes.

The Structure of Chromatin and Its Influence on Gene Regulation

The Structure of Chromatin and Its Influence on Gene Regulation
Author: Morgan Welsh Bernier
Publisher:
Total Pages: 139
Release: 2014
Genre:
ISBN:

Eukaryotic DNA is organized into a structural polymer called chromatin which ultimately controls important DNA processing functions such as transcription, DNA repair and DNA replication. The fundamental unit of chromatin is the nucleosome which is made up of about 146 base pairs wrapped around a histone core. The histone core contains 2 copies each of the histones H2A, H2B, H3 and H4. Long strings of nucleosomes compact into higher order structures which are not well known, but play a pivotal role in DNA accessibility. There are many factors that affect higher order structure and compaction of chromatin including inter and intra nucleosome interactions, incorporation of linker histones (H1), and post translational modifications. This dissertation includes a detailed study of some of these mechanisms. The first study looks at the H3 N-terminal tail which is long, unstructured and heavily modified in vivo . Using Electron Paramagnetic Resonance and site directed spin labeling; we were able to observe the dynamics of the H3 tail within compacted 17-mer nucleosome arrays. We find that these tails maintain their mobility as the arrays compact and self-associate despite previous studies that suggested these tails make inter- and intra-nucleosome contacts during compaction. We conclude that these contacts are transient and permit the tails to maintain mobility and accessibility.

Transcriptional Control of Neural Crest Development

Transcriptional Control of Neural Crest Development
Author: Brian L. Nelms
Publisher: Morgan & Claypool Publishers
Total Pages: 227
Release: 2010
Genre: Science
ISBN: 161504048X

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