Open Access. Powered by Scholars. Published by Universities.®

Medicine and Health Sciences Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 30 of 38

Full-Text Articles in Medicine and Health Sciences

Characterization Of Higher-Order Chromatin Structure In Bone Differentiation And Breast Cancer: A Dissertation, Ahmet Rasim Barutcu Feb 2016

Characterization Of Higher-Order Chromatin Structure In Bone Differentiation And Breast Cancer: A Dissertation, Ahmet Rasim Barutcu

GSBS Dissertations and Theses

Higher-order genome organization is important for the regulation of gene expression by bringing different cis-regulatory elements and promoters in proximity. The establishment and maintenance of long-range chromatin interactions occur in response to cellular and environmental cues with the binding of transcription factors and chromatin modifiers. Understanding the organization of the nucleus in differentiation and cancer has been a long standing challenge and is still not well-understood. In this thesis, I explore the dynamic changes in the higher-order chromatin structure in bone differentiation and breast cancer. First, we show dynamic chromatin contact between a distal regulatory element and the promoter of ...


Gli-Ikbke Requirement In Kras-Induced Pancreatic Tumorigenesis: A Dissertation, Mihir S. Rajurkar Nov 2014

Gli-Ikbke Requirement In Kras-Induced Pancreatic Tumorigenesis: A Dissertation, Mihir S. Rajurkar

GSBS Dissertations and Theses

Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive human malignancies, is thought to be initiated by KRAS activation. Here, we find that transcriptional activation mediated by the GLI family of transcription factors, although dispensable for pancreatic development, is required for KRAS induced pancreatic transformation. Inhibition of GLI using a dominant-negative repressor (Gli3T) inhibits formation of precursor Pancreatic Intraepithelial Neoplasia (PanIN) lesions in mice, and significantly extends survival in a mouse model of PDAC. Further, ectopic activation of the GLI1/2 transcription factors in mouse pancreas accelerates KRAS driven tumor formation and reduces survival, underscoring the importance of GLI transcription ...


The Three-Dimensional Structure Of The Cystic Fibrosis Locus: A Dissertation, Emily M. Smith Nov 2014

The Three-Dimensional Structure Of The Cystic Fibrosis Locus: A Dissertation, Emily M. Smith

GSBS Dissertations and Theses

The three dimensional structure of the human genome is known to play a critical role in gene function and expression. I used chromosome conformation capture (3C) and 3C-carbon copy (5C) techniques to investigate the three-dimensional structure of the cystic fibrosis transmembrane conductance regulator (CFTR) locus. This is an important disease gene that, when mutated, causes cystic fibrosis. 3C experiments identified four distinct looping elements that contact the CFTR gene promoter only in CFTR-expressing cells. Using 5C, I expanded the region of study to a 2.8 Mb region surrounding the CFTR gene. The 5C study shows 7 clear topologically associating ...


Identification And Characteristics Of Factors Regulating Hepatocellular Carcinoma Progression And Metastasis: A Dissertation, Leanne G. Ahronian Mar 2014

Identification And Characteristics Of Factors Regulating Hepatocellular Carcinoma Progression And Metastasis: A Dissertation, Leanne G. Ahronian

GSBS Dissertations and Theses

Hepatocellular carcinoma (HCC) is a common malignancy of the liver that is one of the most frequent causes of cancer-related death in the world. Surgical resection and liver transplantation are the only curative options for HCC, and tumor invasion and metastasis render many patients ineligible for these treatments. Identification of the mechanisms that contribute to invasive and metastatic disease may enlighten therapeutic strategies for those not eligible for surgical treatments. In this dissertation, I describe two sets of experiments to elucidate mechanisms underlying HCC dissemination, involving the activities of Krüppel-like factor 6 and a particular p53 point mutation, R172H.

Gene ...


Intestine Homeostasis And The Role Of Tumor Suppressor Gene 101 In Drosophila Melanogaster: A Dissertation, Madhurima Chatterjee Dec 2011

Intestine Homeostasis And The Role Of Tumor Suppressor Gene 101 In Drosophila Melanogaster: A Dissertation, Madhurima Chatterjee

GSBS Dissertations and Theses

Tissue homeostasis in the adult Drosophila melanogaster intestine is maintained by controlling the proper balance of stem cell self-renewal and differentiation. In the adult fly midgut, intestinal stem cells (ISCs) are the only dividing cells and their identity maintenance is crucial to the proper functioning of the fly gut. Various pathways such as Notch, JAK-STAT and Wingless are known to regulate ISC division and differentiation.

Here I used a pathogen feeding model to study conditions that accelerate ISC division and guide intestinal cell differentiation favoring enterocyte development. I also examined the role of Tumor Suppressor Gene 101 (TSG101) in ISC ...


Chromosome-Biased Binding And Function Of C. Elegans Drm Complex, And Its Role In Germline Sex-Silencing: A Dissertation, Tomoko M. Tabuchi Jul 2011

Chromosome-Biased Binding And Function Of C. Elegans Drm Complex, And Its Role In Germline Sex-Silencing: A Dissertation, Tomoko M. Tabuchi

GSBS Dissertations and Theses

DRM is a conserved transcription factor complex that includes E2F/DP and pRB family proteins and plays important roles in the cell cycle and cancer. Recent work has unveiled a new aspect of DRM function in regulating genes involved in development and differentiation. These studies, however, were performed with cultured cells and a genome-wide study involving intact organisms undergoing active proliferation and differentiation was lacking. Our goal was to extend the knowledge of the role of DRM in gene regulation through development and in multiple tissues. To accomplish this, we employed genomic approaches to determine genome-wide targets of DRM using ...


Regulation Of Cellular And Hiv-1 Gene Expression By Positive Transcription Elongation Factor B: A Dissertation, Siobhan O'Brien Oct 2010

Regulation Of Cellular And Hiv-1 Gene Expression By Positive Transcription Elongation Factor B: A Dissertation, Siobhan O'Brien

GSBS Dissertations and Theses


RNA polymerase II-mediated transcription of HIV-1 genes depends on positive transcription elongation factor b (P-TEFb), the complex of cyclin T1 and CDK9. Recent evidence suggests that regulation of transcription by P-TEFb involves chromatin binding and modifying factors. To determine how P-TEFb may connect chromatin remodeling to transcription, we investigated the relationship between P-TEFb and histone H1. We show that P-TEFb interacts with H1 and that H1 phosphorylation in cell culture correlates with P-TEFb activity. Importantly, P-TEFb also directs H1 phosphorylation during Tat transactivation and wild type HIV-1 infection. Our results also show that P-TEFb phosphorylates histone H1.1 at a ...


A Multiparameter Network Reveals Extensive Divergence Between C. Elegans Bhlh Transcription Factors: A Dissertation, Christian A. Grove Sep 2009

A Multiparameter Network Reveals Extensive Divergence Between C. Elegans Bhlh Transcription Factors: A Dissertation, Christian A. Grove

GSBS Dissertations and Theses

It has become increasingly clear that transcription factors (TFs) play crucial roles in the development and day-to-day homeostasis that all biological systems experience. TFs target particular genes in a genome, at the appropriate place and time, to regulate their expression so as to elicit the most appropriate biological response from a cell or multicellular organism. TFs can often be grouped into families based on the presence of similar DNA binding domains, and these families are believed to have expanded and diverged throughout evolution by several rounds of gene duplication and mutation. The extent to which TFs within a family have ...


Delineating The C. Elegans Microrna Regulatory Network: A Dissertation, Natalia Julia Martinez Apr 2009

Delineating The C. Elegans Microrna Regulatory Network: A Dissertation, Natalia Julia Martinez

GSBS Dissertations and Theses

Metazoan genomes contain thousands of protein-coding and non-coding RNA genes, most of which are differentially expressed, i.e., at different locations, at different times during development, or in response to environmental signals. Differential gene expression is achieved through complex regulatory networks that are controlled in part by two types of trans-regulators: transcription factors (TFs) and microRNAs (miRNAs). TFs bind to cis-regulatory DNA elements that are often located in or near their target genes, while microRNAs hybridize to cis-regulatory RNA elements mostly located in the 3’ untranslated region (3’UTR) of their target mRNAs.

My work in the ...


An Omega-Based Bacterial One-Hybrid System For The Determination Of Transcription Factor Specificity, Marcus Blaine Noyes Mar 2009

An Omega-Based Bacterial One-Hybrid System For The Determination Of Transcription Factor Specificity, Marcus Blaine Noyes

GSBS Dissertations and Theses

From the yeast genome completed in 1996 to the 12 Drosophilagenomes published earlier this year; little more than a decade has provided an incredible amount of genomic data. Yet even with this mountain of genetic information the regulatory networks that control gene expression remain relatively undefined. In part, this is due to the enormous amount of non-coding DNA, over 98% of the human genome, which needs to be made sense of. It is also due to the large number of transcription factors, potentially 2,000 such factors in the human genome, which may contribute to any given network directly ...


Functional Interaction Of Bpv-1 E2 With The Papillomavirus Genome: A Dissertation, Suzanne Marie Melanson Feb 2009

Functional Interaction Of Bpv-1 E2 With The Papillomavirus Genome: A Dissertation, Suzanne Marie Melanson

GSBS Dissertations and Theses

The bovine papillomavirus type 1 E2 protein is a multifunctional early viral protein with roles in all phases of the cell cycle. E2 is required during G1 as a transcription factor, in S phase to initiate viral replication and during mitosis to tether the viral genome to dividing DNA. The viral genome contains 17 E2 binding sites, the majority of which are concentrated in the long control region (LCR), a regulatory region that is upstream of the viral coding sequence. The role of these binding sites has been explored in vitro using small plasmids and E1 and E2 proteins expressed ...


Role Of Supervillin, A Membrane Raft Protein, In Cytoskeletal Organization And Invadopodia Function, Jessica Lynn Crowley Feb 2009

Role Of Supervillin, A Membrane Raft Protein, In Cytoskeletal Organization And Invadopodia Function, Jessica Lynn Crowley

GSBS Dissertations and Theses

Crucial to a cell’s ability to migrate is the organization of its plasma membrane and associated proteins in a polarized manner to interact with and respond to its surrounding environment. Cells interact with the extracellular matrix (ECM) through specialized contact sites, including podosomes and invadopodia. Tumor cells use F-actin-rich invadopodia to degrade ECM and invade tissues; related structures, termed podosomes, are sites of dynamic ECM interaction and degradation. We show here that supervillin (SV), a peripheral membrane protein that binds F-actin and myosin II,reorganizes the actin cytoskeleton and potentiates invadopodial function. Overexpressed SV increases the number of F-actin ...


Checkpoint Regulation Of S-Phase Transcription: A Dissertation, Chaitali Dutta Sep 2008

Checkpoint Regulation Of S-Phase Transcription: A Dissertation, Chaitali Dutta

GSBS Dissertations and Theses

The DNA replication checkpoint transcriptionally up-regulates genes that allow cells to adapt to and survive replication stress. Our results show that, in the fission yeast Schizosaccharomyces pombe, the replication checkpoint regulates the entire G1/S transcriptional program by directly regulating MBF (aka DSC1), the G1/S transcription factor. Instead of initiating a checkpoint-specific transcriptional program, the replication checkpoint targets MBF to maintain the normal G1/S transcriptional program during replication stress. We propose a mechanism for this regulation, based on in vitrophosphorylation of the Cdc10 subunit of MBF by the Cds1 replication-checkpoint kinase. Substitution of two potential phosphorylation sites ...


Analysis Of Cpeb Family Protein Member Cpeb4 Function In Mammalian Neurons: A Dissertation, Ming-Chung Kan Jun 2008

Analysis Of Cpeb Family Protein Member Cpeb4 Function In Mammalian Neurons: A Dissertation, Ming-Chung Kan

GSBS Dissertations and Theses

Local protein synthesis is required for long-term memory formation in the brain. One protein family, Cytoplasmic Polyadenylation Element binding Protein (CPEB) that regulates protein synthesis is found to be important for long-term memory formation possibly through regulating local protein synthesis in neurons. The well-studied member of this family, CPEB1, mediates both translational repression and activation of its target mRNAs by regulating mRNA polyadenylation. Mouse with CPEB1 KO shows defect in memory extinction but not long-term memory formation. Three more CPEB1 homologs (CPEB2-4) are identified in mammalian system. To test if CPEB2-4 may have redundant role in replacing CPEB1 in mediating ...


Regulation Of The Nf-Кb Precursor Relish By The Drosophila I-Кb Kinase Complex: A Dissertation, Deniz Erturk Hasdemir May 2008

Regulation Of The Nf-Кb Precursor Relish By The Drosophila I-Кb Kinase Complex: A Dissertation, Deniz Erturk Hasdemir

GSBS Dissertations and Theses

The innate immune system is the first line of defense against infectious agents. It is essential for protection against pathogens and stimulation of long-term adaptive immune responses. Therefore, deciphering the mechanisms of the innate immune system is crucial for understanding the integrated systems of host defense against microbial infections, which is conserved from insects to humans.

Despite lacking a conventional adaptive immune system, insects can mount a robust immune response against a wide array of microbial pathogens. These innate immune mechanisms have been widely studied in Drosophila melanogaster, because of the model system’s powerful genetic, genomic and molecular tools ...


A Genetic Analysis Of Genomic Stability In Caenorhabditis Elegans: A Dissertation, Melissa M. Auclair Sep 2007

A Genetic Analysis Of Genomic Stability In Caenorhabditis Elegans: A Dissertation, Melissa M. Auclair

GSBS Dissertations and Theses

In humans, Bloom’s Syndrome is caused by a mutation of the RecQ helicase BLM. Patients with Bloom’s Syndrome exhibit a high amount of genomic instability which results in a high incidence of cancer. Though Bloom’s Syndrome has been intensively studied, there are still many questions about the function of BLM which need to be answered. While it is clear that loss of BLM increases genomic instability, the other effects of genomic instability on the organism aside from cancer such as a potential effect on aging, have yet to be elucidated.

In Chapter II, I identify new phenotypes ...


Functional And Structural Dissection Of The Swi/Snf Chromatin Remodeling Complex: A Dissertation, Xiaofang Yang May 2007

Functional And Structural Dissection Of The Swi/Snf Chromatin Remodeling Complex: A Dissertation, Xiaofang Yang

GSBS Dissertations and Theses

The yeast SWI/SNF complex is the prototype of a subfamily of ATP-dependent chromatin remodeling complexes. It consists of eleven stoichiometric subunits including Swi2p/Snf2p, Swi1p, Snf5p, Swi3p, Swp82p, Swp73p, Arp7p, Arp9p, Snf6p, Snf11p, and Swp29p, with a molecular weight of 1.14 mega Daltons. Swi2p/Snf2p, the catalytic subunit of SWI/SNF, is evolutionally conserved from yeast to human cells. Genetic evidence suggests that SWI/SNF is required for the transcriptional regulation of a subset of genes, especially inducible genes. SWI/SNF can be recruited to target promotors by gene specific activators, and in some cases, SWI/SNF facilitates ...


Plagl2 Cooperates In Leukemia Development By Upregulating Mpl Expression: A Dissertation, Sean F. Landrette Jun 2006

Plagl2 Cooperates In Leukemia Development By Upregulating Mpl Expression: A Dissertation, Sean F. Landrette

GSBS Dissertations and Theses

Chromosomal alterations involving the RUNXI or CBFB genes are specifically and recurrently associated with human acute myeloid leukemia (AML). One such chromosomal alteration, a pericentric inversion of chromosome 16, is present in the majority of cases of the AML subtype M4Eo. This inversion joins CBFB with the smooth muscle myosin gene MYH11 creating the fusion CBFB-MYH11. Knock-in studies in the mouse have demonstrated that expression of the protein product of the Cbfb-MYH11fusion, Cbfβ-SMMHC, predisposes mice to AML and that chemical mutagenesis both accelerates and increases the penetrance of the disease (Castilla et al., 1999). However, the mechanism of transformation ...


Sox13, A Γδ T Cell-Specific Gene, Is A Wnt-Signaling Antagonist Regulating T Cell Development: A Dissertation, Heather J. Melichar May 2006

Sox13, A Γδ T Cell-Specific Gene, Is A Wnt-Signaling Antagonist Regulating T Cell Development: A Dissertation, Heather J. Melichar

GSBS Dissertations and Theses

Mature αβ and γδ T cells arise from a common precursor population in the thymus. Much debate has focused on the mechanism of T cell lineage choice made by these multi-potential precursor cells. It is widely believed that the decision of these precursor cells to commit to the γδ or αβ T cell lineages is regulated primarily by a specific instructive signal relayed through the appropriate T cell receptor. Contrary to this model, we present evidence for a TCR-independent lineage commitment process. Comparison of global gene expression profiles from immature αβ and γδ lineage thymocytes identified Sox13, an HMG-box transcription ...


Transcriptional Regulation During Adipocyte Differentiation: A Role For Swi/Snf Chromatin Remodeling Enzymes: A Dissertation, Nunciada Salma Mar 2006

Transcriptional Regulation During Adipocyte Differentiation: A Role For Swi/Snf Chromatin Remodeling Enzymes: A Dissertation, Nunciada Salma

GSBS Dissertations and Theses

Chromatin has a compact organization in which most DNA sequences are structurally inaccessible and functionally inactive. Reconfiguration of thechromatir required to activate transcription. This reconfiguration is achieved by the action of enzymes that covalently modify nucleosomal core histones, and by enzymes that disrupt histone-DNA interactions via ATP hydrolysis.

TheSWI/SNF family of ATP-dependent chromatin remodeling enzymes has been implicated not only in gene activation but also in numerous cellular processes including differentiation, gene repression, cell cycle control, recombination and DNA repair. PPARγ, C/EBPα and C/EBPβ are transcription factors with well established roles in adipogenesis. Ectopical expression of each ...


Regulation Of Life Span By Daf-16/Forkhead Transcription Factor In Caenorhabditis Elegans: A Dissertation, Seung Wook Oh Oct 2005

Regulation Of Life Span By Daf-16/Forkhead Transcription Factor In Caenorhabditis Elegans: A Dissertation, Seung Wook Oh

GSBS Dissertations and Theses

The insulin/IGF-1 signaling pathway plays a pivotal role in life span regulation in diverse organisms. In Caenorhabditis elegans, a PI 3-kinase signaling cascade downstream of DAF-2, an ortholog of the mammalian insulin and insulin-like growth factor-1 (IGF-1) receptor, negatively regulates DAF-16/forkhead transcription factor. DAF-16 then regulates a wide variety of genes involved in longevity, stress response, metabolism and development. DAF-16 also receives signals from other pathways regulating life span and development. However, the precise mechanism by which DAF-16 directs multiple functions is poorly understood.

First, in Chapter II, we demonstrate that JNK is a novel positive regulator of ...


Regulation Of Cell Growth And Differentiation Within The Context Of Nuclear Architecture By The Runx2 Transcription Factor: A Dissertation, Daniel W. Young Sep 2005

Regulation Of Cell Growth And Differentiation Within The Context Of Nuclear Architecture By The Runx2 Transcription Factor: A Dissertation, Daniel W. Young

GSBS Dissertations and Theses

The Runx family of transcription factors performs an essential role in animal development by controlling gene expression programs that mediate cell proliferation, growth and differentiation. The work described in this thesis is concerned with understanding mechanisms by which Runx proteins support this program of gene expression within the architectural context of the mammalian cell nucleus. Multiple aspects of nuclear architecture are influenced by Runx2 proteins including sequence-specific DNA binding at gene regulatory regions, organization of promoter chromatin structure, and higher-order compartmentalization of proteins in nuclear foci. This work provides evidence for several functional activities of Runx2 in relation to architectural ...


The Identification Of Cooperating Mutations In Tal1-Mediated Leukemia In The Mouse: A Dissertation, Jennifer Ann Calvo Sep 2005

The Identification Of Cooperating Mutations In Tal1-Mediated Leukemia In The Mouse: A Dissertation, Jennifer Ann Calvo

GSBS Dissertations and Theses

A sequential series of mutational events is necessary for the development of leukemia. The misexpression of TAL1, a basic helix-loop-helix (bHLH) transcription factor, is the most common mutation in T cell acute lymphoblastic leukemia (T-ALL). Tal1 transgenic mice develop leukemia with a long latency and incomplete penetrance indicating additional mutations are necessary to develop disease. To investigate additional mutational events that potentially contribute to TAL1-expressing T-ALL patients, we sought to identify cooperating mutations in Tal1 transgenic mice. Clinical studies implicated the loss of the INK4a/ARF locus, which encodes two tumor suppressors, p16INK4a and p14ARF, in the majority ...


Egr-2 And Pd-1 Are Required For Induction And Maintenance Of T Cell Anergy: A Dissertation, Kenneth D. Bishop Jul 2005

Egr-2 And Pd-1 Are Required For Induction And Maintenance Of T Cell Anergy: A Dissertation, Kenneth D. Bishop

GSBS Dissertations and Theses

The prevalence of diabetes is approaching epidemic proportions worldwide. There is currently no cure for type 1 diabetes, and successful treatment requires constant monitoring of blood sugars and use of exogenous insulin to prevent hyperglycemia. Diabetes will be curable when pancreatic β-islet cells can be transplanted into diabetes patients without requiring long-term immunosuppression. This will require learning more about the induction of functional tolerance, a state that maintains the competence of the immune system to most antigens but protects graft-specific antigens from immune rejection, permitting transplantation. One known mechanism of peripheral tolerance is T cell anergy, a phenotype of hypo-reponsiveness ...


Regulation And Function Of Runx2 During Chondrogenic And Osteogenic Differentiation: A Dissertation, Christopher J. Lengner Dec 2004

Regulation And Function Of Runx2 During Chondrogenic And Osteogenic Differentiation: A Dissertation, Christopher J. Lengner

GSBS Dissertations and Theses

Members of the Runx family of transcription factors play essential roles in the differentiation and development of several organ systems. Here we address the contribution of the osteoblast-related Runx gene, Runx2, to the osteogenic and chondrogenic differentiation of mesenchymal stem cells. Using a transgenic mouse model, we observe Runx2 transcription through one of its two known promoters (designated P1 in pre-cartilaginous mesenchymal condensations as early as E9.5. Runx2 gene activity is later repressed at the onset of cartilage formation, both in vivo and in vitro, necessitating examination of the regulation and function of Runx2 in mesenchymal stem cells. We ...


Functional And Structural Analysis Of The Yeast Swi/Snf Complex: A Dissertation, Corey Lewis Smith Jul 2004

Functional And Structural Analysis Of The Yeast Swi/Snf Complex: A Dissertation, Corey Lewis Smith

GSBS Dissertations and Theses

Modulating chromatin structure is an important step in maintaining control over the eukaryotic genome. SWI/SNF, one of the complexes belonging to the growing family of ATP-dependent chromatin remodeling enzymes, is involved in controlling the expression of a number of inducible genes whose proper regulation is vital for metabolism and progression through mitosis. The mechanism by which SWI/SNF modulates chromatin structure at the nucleosome level is an important aspect of this regulation. The work in this dissertation focuses on how the Saccharomyces cerevisiae SWI/SNF complex uses the energy of ATP-hydrolysis to alter DNA-histone contacts in nucleosomes. This has ...


Pathways Linking Deregulated Proliferation To Apoptosis: A Dissertation, Harry A. Rogoff Apr 2004

Pathways Linking Deregulated Proliferation To Apoptosis: A Dissertation, Harry A. Rogoff

GSBS Dissertations and Theses

Proper regulation of cellular proliferation is critical for normal development and cancer prevention. Most, if not all, cancers contain mutations in the Rb/E2F pathway, which controls cellular proliferation. Inactivation of the retinoblastoma protein (Rb) can occur through Rb loss, mutation, or inactivation by cellular or viral oncoproteins leading to unrestrained proliferation. This occurs primarily by de-repression and activation of the E2F transcription factors, which promote the transition of cells from the G1to S phase of the cell cycle. In order to protect against loss of growth control, the p53 tumor suppressor is able to induce programmed cell ...


Mechanisms Of Tal1 Induced Leukemia In Mice: A Dissertation, Jennifer Elinor O'Neil Jan 2004

Mechanisms Of Tal1 Induced Leukemia In Mice: A Dissertation, Jennifer Elinor O'Neil

GSBS Dissertations and Theses

Activation of the basic helix-loop-helix (bHLH) gene TAL1 is the most common genetic event seen in both childhood and adult T cell acute lymphoblastic leukemia (T-ALL). Despite recent success in treating T-ALL patients, TAL1 patients do not respond well to current therapies. In hopes of leading the way to better therapies for these patients, we have sought to determine the mechanism(s) of Tal1 induced leukemia in mice. By generating a DNA-binding mutant Tal1 transgenic mouse we have determined that the DNA binding activity of Tal1 is not required to induce leukemia. We have also shown that Tal1 expression in ...


Conserved Nucleosome Remodeling/Histone Deacetylase Complex And Germ/Soma Distinction In C. Elegans: A Dissertation, Yingdee Unhavaithaya Aug 2003

Conserved Nucleosome Remodeling/Histone Deacetylase Complex And Germ/Soma Distinction In C. Elegans: A Dissertation, Yingdee Unhavaithaya

GSBS Dissertations and Theses

A rapid cascade of regulatory events defines the differentiated fates of embryonic cells, however, once established, these differentiated fates and the underlying transcriptional programs can be remarkably stable. Here, we describe two proteins, MEP-1, a novel protein, and LET-418/Mi-2, both of which are required for the maintenance of somatic differentiation in C. elegans. MEP-1 was identified as an interactor of PIE-1, a germ-specific protein required for germ cell specification, while LET-418 is a protein homologous to Mi-2, a core component of the nuc1eosome remodeling/histone deacetylase (NuRD) complex. In animals lacking MEP-1 and LET-418, germline-specific genes become derepressed in ...


The Molecular Mechanisms Of T Cell Clonal Anergy: A Dissertation, John E. Harris Jun 2003

The Molecular Mechanisms Of T Cell Clonal Anergy: A Dissertation, John E. Harris

GSBS Dissertations and Theses

A side effect of generating an immune system for defense against invading pathogens is the potential to develop destructive cells that recognize self-tissues. Typically, through the "education" of developing immune cells, the organism inactivates potentially self-destructive cells, resulting in what is called self-tolerance. I proposed to explore the molecular mechanisms responsible for the induction and maintenance of tolerance. Our lab has developed a model of induced immune tolerance to skin and islet allografts utilizing a donor-specific transfusion of spleen cells and a brief course of anti-CD40L antibody. Because the difficulty in isolation of tolerant T cells from this system is ...