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Articles 151 - 180 of 1126
Full-Text Articles in Biology
The Clinical Significance And Genetic Origin Of P14arf, Anna Louise Grobelny Guthrie
The Clinical Significance And Genetic Origin Of P14arf, Anna Louise Grobelny Guthrie
Arts & Sciences Graduate Student Theses and Dissertations
The p14ARF tumor suppressor is the second most commonly mutated gene in Non-Small Cell Lung Cancer (NSCLC). p14ARF (p19ARF in mice) is encoded by the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene. The p14ARF tumor suppressor is known to play a fundamental role in cancer progression by regulating senescence, apoptosis, and proliferation. The primary function of p14ARF is to respond to oncogenic signals and activate the p53 tumor suppressor by inhibiting and sequestering the HDM2 (MDM2) oncogene. However, recent studies have uncovered multiple p53-independent functions of p14ARF, opening the door to a myriad of possible vulnerabilities in p14ARF-mutant tumors. Many current …
Elucidating The First Protective Mutation From Inherited Alzheimer’S Disease - Apolipoprotein E3 Christchurch (Apoe3ch) And Insights Into Apoe Ligand-Receptor Interactions, Yun Chen
Arts & Sciences Graduate Student Theses and Dissertations
Alzheimer’s disease (AD) is the major cause of dementia. An inherited form of AD (dominant inherited AD) starts much earlier in life, often in the fourth and fifth decade. A recent case report described an individual who was resistant to dominantly inherited AD caused by a PSEN1-E280A mutation and was a homozygous carrier of the APOE3 Christchurch (APOE3ch) variant. A clear separation between amyloid and tau pathology occurred in this unique AD case. However, whether APOE3ch contributed to the protective effect remains unclear. In this thesis, we generated a humanized APOE3ch knock-in mouse and crossed it to an amyloid-β (Aβ) …
Systemic Activation Of The Axon Degeneration Executioner Sarm1 Triggers Acute Hyperglycemia, Lillian Spatz
Systemic Activation Of The Axon Degeneration Executioner Sarm1 Triggers Acute Hyperglycemia, Lillian Spatz
Arts & Sciences Graduate Student Theses and Dissertations
Communication between the nervous system and metabolic tissues directs whole body homeostasis. It is well understood that peripheral tissues respond to neural stimulation or inhibition to modulate energy usage and storage, hormone release, and stress pathways, but the neuroendocrine circuits that drive these outcomes remain ill-defined. Our lab identified sterile alpha and TIR motif containing 1 (SARM1) as the central executioner of axon degeneration in injury and disease models. We found that SARM1 is activated by an elevated NMN/NAD+ ratio and that nicotinamide analogs, including 3-AP and vacor, are converted to NMN-like intermediates that directly bind to SARM1, mimicking the …
Molecular Mechanisms Behind Methionine-Derived Glucosinolate Diversity In Brassica Plants, Vivian Kitainda
Molecular Mechanisms Behind Methionine-Derived Glucosinolate Diversity In Brassica Plants, Vivian Kitainda
Arts & Sciences Graduate Student Theses and Dissertations
In Brassica plants, glucosinolates are a diverse class of natural products that serve as plant defense molecules. Their structural diversity comes from the use of amino acids as precursors and elongation of side chains by up to nine carbons, as well as further chemical modifications. Aliphatic methionine-derived glucosinolates are the most abundant form of these compounds. Although both elongation and chemical modification of amino acid sidechains are important for methionine-glucosinolate diversity, its elongation process has not been well described. The chain elongation enzyme methylthioalkylmalate synthase (MAMS) functions as the glucosinolate pathway gatekeeper through its substrate specificity. The x-ray crystal structure …
Developing Computational And Experimental Tools For Investigating Intrinsically Disordered Proteins And Biomolecular Condensates, Daniel Griffith
Developing Computational And Experimental Tools For Investigating Intrinsically Disordered Proteins And Biomolecular Condensates, Daniel Griffith
Arts & Sciences Graduate Student Theses and Dissertations
Intrinsically disordered proteins and protein regions (IDPs) compose a significant portion of eukaryotic proteomes yet remain relatively understudied. Unlike folded domains, IDPs lack a single fixed three-dimensional structure and instead are defined by a dynamic conformational ensemble. Despite this structural heterogeneity, IDPs carry out vital roles within the cell. IDPs are particularly important in cellular signaling and regulation, owing to their ability to mediate molecular interactions with a variety of affinities and specificities. Additionally, some IDPs drive the formation of higher-order non-stoichiometric assemblies called biomolecular condensates. This dissertation focuses on the development of a variety of computational and experimental tools …
Cellular And Molecular Basis Of Cd4+ T Cell Help At The Effector Phase During Immunotherapy Of Mhc-Ii Negative Tumors, Samuel Oche Ameh
Cellular And Molecular Basis Of Cd4+ T Cell Help At The Effector Phase During Immunotherapy Of Mhc-Ii Negative Tumors, Samuel Oche Ameh
Arts & Sciences Graduate Student Theses and Dissertations
Immune checkpoint therapies (ICT) have shown promise in treating solid tumors, providing cures and durable protection in some cases. However, only a subset of patients benefits from ICT, indicating a need for a deeper understanding of the requirements for successful therapy. In both mice and humans, αβ T cells are key mediators of spontaneous and ICT-induced anti-tumor responses. While the anti-tumor roles of CD8+ T cells are well-studied, the role of CD4+ T cells, particularly in ICT for MHC-II negative tumors, is less understood. New insights into how CD4+ T cells modulate CD8+ T cells during ICT may lead to …
Discovering And Characterizing Conserved Anthelmintic Targets In The Early Parasitic Stages Of Gastrointestinal Nematodes, Hyeim Jung
Arts & Sciences Graduate Student Theses and Dissertations
Gastrointestinal nematodes (GINs) collectively infect 1.5 billion people, leading to mortality and various forms of morbidity in humans and hindering normal development in children. GINs also diminish the productivity of food animals, which are crucial for economic and nutritional well-being, particularly in developing countries. Currently, the world still primarily relies on only a few drug classes for global de-worming of GINs in humans and animals. However, the high rate of reinfection, disappointing treatment success rates, and increasing drug resistance make GINs one of the most important contributors to promoting and maintaining global poverty. This highlights the urgent need for more …
Effects Of Hypoxia On Monocyte Differentiation And Macrophage Specification During Ischemic Heart Injury, Farid Faridovich Kadyrov
Effects Of Hypoxia On Monocyte Differentiation And Macrophage Specification During Ischemic Heart Injury, Farid Faridovich Kadyrov
Arts & Sciences Graduate Student Theses and Dissertations
Myocardial infarction (MI) occurs following cessation of blood flow to an area of the heart and leads to ischemia, cardiomyocyte death, and inflammation. Chronically, MI initiates a compensatory process referred to as left ventricular remodeling, which is characterized by cardiomyocyte hypertrophy, fibrosis, and a decline in heart function. Left ventricular remodeling is central to the pathogenesis of heart failure. During myocardial infarction, Ly6chigh CCR2+ monocytes enter the heart and differentiate into a variety of macrophage populations including inflammatory CCR2+ macrophages. Resident cardiac macrophages are also present within the heart at homeostasis. Previous research from several groups has shown that once …
Aging Antiviral Immunity In The Central Nervous System: Mechanisms And Implications, Artem D. Arutyunov
Aging Antiviral Immunity In The Central Nervous System: Mechanisms And Implications, Artem D. Arutyunov
Arts & Sciences Graduate Student Theses and Dissertations
The complex interplay between aging, neuroinflammation, and neuroimmune responses has become increasingly evident in recent years. Microglia, the resident immune cells of the central nervous system (CNS), play a pivotal role in maintaining neural homeostasis and responding to neuroinflammatory triggers. This dissertation focuses on the role that aging plays in microglial activation and neuroinflammation, specifically in the context of West Nile Virus (WNV) encephalitis. While the incidence of WNV is consistent across age groups, the risk of West Nile Neuroinvasive Disease (WNND), a serious complication of WNV infection, increases with advanced age. Using mouse models of WNV infection, our group …
Epigenetic Dynamics In Zebrafish Development And Regeneration, Yujie Chen
Epigenetic Dynamics In Zebrafish Development And Regeneration, Yujie Chen
Arts & Sciences Graduate Student Theses and Dissertations
Understanding the mechanisms that underlie cell fate and status decisions remains a complex task in biological research. Despite sharing identical genetic content, cells can differentiate into diverse types or remain in different statuses based on epigenetic dynamics. Here, I have structured my thesis into two distinct but interconnected parts, each focusing on a specific aspect of epigenetic control during zebrafish development and regeneration. The first part of the thesis focuses on the differentiation of pigment cells from neural crest cells to understand how the same progenitor cell population can bifurcate into two different pigment cell lineages. Through a comprehensive analysis …
Employing Single-Nucleus Rna-Seq To Uncover Genetic Factors Of Alzheimer Disease, Logan Brase
Employing Single-Nucleus Rna-Seq To Uncover Genetic Factors Of Alzheimer Disease, Logan Brase
Arts & Sciences Graduate Student Theses and Dissertations
Alzheimer’s disease (AD) stands as a daunting global health challenge, affecting millions of individuals worldwide. This burden will only intensify with an aging global population. Despite significant advances in understanding AD, further exploration is needed to enhance the development of treatments and therapeutics. Particularly, I am interested in identifying the molecular pathways involved and the cell types mediating the etiology of AD. This work underscores the ability of single nucleus RNA-seq to investigate these pathways at the cell-type level and mitigate many of the hurdles limiting the successful development of treatments for AD, including genetic heterogeneity and translation of discoveries …
Understanding The Relationship Between Genetic And Epigenetic Variation At A Species And Individual Level, Kara Quaid
Understanding The Relationship Between Genetic And Epigenetic Variation At A Species And Individual Level, Kara Quaid
Arts & Sciences Graduate Student Theses and Dissertations
Genetic sequences and epigenetic features work together to regulate gene expression, which can vary across species, individuals, and cell-types. Understanding this relationship between genetics and epigenetics is a key step to revealing the connection between genotype and phenotype on a systematic, genome-wide level. The first chapter of my thesis outlines the ways genetic variation and epigenetic variation may interact to shape gene regulation across scales, as well as how we can question it further. One of the most studied mechanisms is genetic variation that has a direct impact on epigenetic variation. At the species level, it is documented that species-specific …
Transcriptional Precision In Photoreceptor Development And Diseases - Lessons From The Retinal Transcription Factor Crx, Yiqiao Zheng
Transcriptional Precision In Photoreceptor Development And Diseases - Lessons From The Retinal Transcription Factor Crx, Yiqiao Zheng
Arts & Sciences Graduate Student Theses and Dissertations
Precise gene expression programs are foundational to organism development and homeostasis. Transcription factors play a central role in establishing and maintaining these programs. Large-scale transcriptomic studies have generated parts lists of transcription factors. However, these descriptive works rarely formulate a cohesive model of how these transcription factors work together to support a functional organism. Mutations that affect transcription factor functions can lead to a broad range of human diseases. Therefore, it is crucial to understand the principles that transcription factors achieve spatial, temporal, and quantitative precision in their regulated gene expression programs. I have investigated transcriptional regulation in rod and …
Novel Bioinformatics Tools For Biomarker Discovery In Prostate Cancer, Jace Webster
Novel Bioinformatics Tools For Biomarker Discovery In Prostate Cancer, Jace Webster
Arts & Sciences Graduate Student Theses and Dissertations
Prostate cancer (PCa) accounts for 29% of all expected cancer diagnoses in men in 2024, but patients presenting with different disease stages can have significantly different outcomes. Patients with indolent PCa may experience little to no impact on their quality of life and have a 5-year survival as high as 98%, but progression to aggressive disease causes 5-year survival to plummet to 30%. Patients with the most lethal form of the disease, metastatic castration-resistant PCa (mCRPC), have a median survival of only 5.5 months if they become resistant to treatment. Due to this clinical heterogeneity, it is critical to quickly …
Vascular Electrophysiology And Pathogenic Consequences Of Cardiovascular Katp Channel Mutations, Alex Hanson
Vascular Electrophysiology And Pathogenic Consequences Of Cardiovascular Katp Channel Mutations, Alex Hanson
Arts & Sciences Graduate Student Theses and Dissertations
The complex cardiovascular disorder Cantú Syndrome (CS) arises from gain-of-function (GoF) mutations in either KCNJ8 or ABCC9, the genes encoding the Kir6.1 and SUR2 subunits of cardiovascular ATP-sensitive potassium (KATP) channels, respectively. CS involves an array of cardiovascular pathologies, including cardiac hypertrophy and hypercontractility, low systemic vascular resistance, and excessively compliant, dilated, and tortuous vessels. Together, the latter features exemplify the hypomyotonic and hyperelastic components of CS vasculopathy. It was recently established that CS vasculopathy drives the associated cardiac pathologies, which are observed even in the absence of cardiac KATP GoF. In this thesis, I carried out experiments to determine …
Inducible Crispr-Targeted ‘Knockdown’ Of Human Gut Bacteroides In Mice Reveals Glycan Utilization Strategies, Zachary Beller
Inducible Crispr-Targeted ‘Knockdown’ Of Human Gut Bacteroides In Mice Reveals Glycan Utilization Strategies, Zachary Beller
Arts & Sciences Graduate Student Theses and Dissertations
Learning how members of the human gut microbiota compete and cooperate for dietary nutrients, such as fiber-associated glycans, should help facilitate development of more precise nutritional recommendations for improving health. To model how bacteria prioritize the utilization of different fiber glycans in the mammalian gut, germ-free mice were colonized with a 13-member consortium of cultured, genome-sequenced human bacterial strains, including seven Bacteroides species. Animals were fed a Western diet supplemented with pea fiber. Once the consortium had time to assemble, an inducible CRISPR-based system was used to deplete the absolute abundance of Bacteroides thetaiotaomicron or B. cellulosilyticus by 10- to …
Role Of Integrase-Pp2a Interaction In Human T-Cell Leukemia Virus Type-1 Replication And Pathogenesis, Shayna Turbin
Role Of Integrase-Pp2a Interaction In Human T-Cell Leukemia Virus Type-1 Replication And Pathogenesis, Shayna Turbin
Senior Honors Papers / Undergraduate Theses
Human T-cell leukemia virus type-1 (HTLV-1) is an oncogenic retrovirus that causes multiple disorders, including adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. HTLV-1 retroviral integrase binds to the regulatory B’56γ subunit of the host cell Protein Phosphatase 2A (PP2A). Integrase contains a highly conserved LxxIxE motif that is essential for binding, which increases integration efficiency and facilitates HTLV-1 hijack of host cell machinery. We aim to understand how mutations introduced in the highly conserved binding site can affect viral particle production and infectivity. We transfected 729B human lymphoblastoid cells and 293T cells with mutant and wildtype virus. Mutations L213A, …
Antimicrobial Mechanisms Of Human Lipocalin-2, Lindsey Steinberg
Antimicrobial Mechanisms Of Human Lipocalin-2, Lindsey Steinberg
Arts & Sciences Graduate Student Theses and Dissertations
Lipocalin-2 (Lcn2, also known as siderocalin or neutrophil gelatinase-associated lipocalin) is an innate immune protein released by neutrophils and epithelial cells at sites of infection. It is understood to limit bacterial growth by restricting access to iron, an essential nutrient, but it does not avidly bind iron in isolation. At least two iron restricting Lcn2 mechanisms are described in the literature. In the prototypical mechanism, Lcn2 binds and prevents uptake of enterobactin, a high affinity iron chelator secreted by E. coli and closely related Enterobacterales. Sequestration of this bacterial siderophore prevents nutritional iron delivery to these pathogens. However, the narrow …
Tracking And Mitigating Imprint Erasure During Human Pluripotent State Transitions, Laura A. Fischer
Tracking And Mitigating Imprint Erasure During Human Pluripotent State Transitions, Laura A. Fischer
Arts & Sciences Graduate Student Theses and Dissertations
Early human embryogenesis is difficult to study due to practical and ethical limitations, but the successful culture of “naïve” human pluripotent stem cells (hPSCs) has expanded our ability to model cells akin to the pre-implantation epiblast. Naïve hPSCs are readily obtained through in vitro resetting of “primed” hPSCs, cells which model the post-implantation epiblast. Naïve hPSCs offer the advantages of modeling the pre-implantation transcriptome and epigenome, the ability to form embryonic and extraembryonic tissues, and the capacity to self-organize into integrated human embryo models. However, a persistent drawback of naïve hPSCs is the loss of parent-specific epigenetic marks, called imprints. …
Evaluating Pathological Tau Spread In Early Alzheimer Disease: Developing A Metric For Tau Positron Emission Tomography Quantifying Tau Spatial Spread, Stephanie Sierra Doering
Evaluating Pathological Tau Spread In Early Alzheimer Disease: Developing A Metric For Tau Positron Emission Tomography Quantifying Tau Spatial Spread, Stephanie Sierra Doering
Arts & Sciences Graduate Student Theses and Dissertations
The overall goal of this dissertation is to gain a better understanding of how pathological tau burden and tau spread are related at early stages of Alzheimer Disease, and whether each tau component is uniquely informative to key elements of AD progression. A spatiotemporal pattern of tau pathological progression is observed in AD and is highly correlated to regional neurodegeneration and domain-specific cognitive impairment. This progression is reflective of two biological processes: the aggregation of tau neurofibrillary tangles in early brain regions (tau burden) as well as the transmission of pathological tau to additional brain regions (tau spread). Positron emission …
Understanding Mechanisms Of Local Adaptation In White Clover (Trifolium Repens L.): Insights From A Phenotypic Cline And Population Genomics, Wen-Hsi Kuo
Arts & Sciences Graduate Student Theses and Dissertations
Rapid global climate change threatens food production and natural ecosystems. Knowledge of the mechanisms by which species adapt to local climates can inform future agriculture and conservation efforts and help to ensure sustainability and resilience of both cultivated and wild species. The overarching goal of this dissertation is to investigate the broad range of adaptive traits and their underlying genetics in wild populations of a widely distributed and polyploid forage plant, white clover. White clover is an ideal system because of its genetic diversity, widespread distribution, and its ability adapt to various environmental stresses through mechanisms that include its well-studied …
Microbial Community Composition And Assembly In Diverse Environmental Systems, Rhiannon Celeste Vargas
Microbial Community Composition And Assembly In Diverse Environmental Systems, Rhiannon Celeste Vargas
Arts & Sciences Graduate Student Theses and Dissertations
Analyzing microbial community responses across systems, particularly in coordinated ways, is critical to informing meaningful community ecology patterns. In Chapter 1, I provide historical contexts to the field of microbial community ecology. In Chapter 2 I have investigated a specific opportunistic pathogen, Staphyloccocus pseudintermedius, by utilizing whole genome sequencing to understand the genomic architecture that contributes to the community structures of S. pseudintermedius found in different environmental niches. We found that unlike other Staphylococcal pathogens, S. pseudintermedius niches are indistinguishable by core and accessory gene architecture. Rather, niches are resolved through the encoding of antimicrobial resistances such as those isolates …
Functions Of Cdc1 In Mediating Cd4+ Help For Cd8+ T Cells, Renee Wu
Functions Of Cdc1 In Mediating Cd4+ Help For Cd8+ T Cells, Renee Wu
Arts & Sciences Graduate Student Theses and Dissertations
Classical dendritic cells (cDCs) are specialized antigen presenting cells that comprise distinct subsets distinguished by transcriptional developmental differences and in the types of immune responses they initiate. Classical type 1 dendritic cells (cDC1) are thought to perform antigen cross-presentation, which is required to prime CD8 T cells, whereas cDC2 have been suggested to be specialized for priming CD4 T cells. CD4 T cell help for CD8 T cell responses has been proposed to be mediated by CD40-dependent licensing of antigen-presenting cells. cDC1 have been suggested as the target of CD4 T cell help on the basis of in vitro analysis …
Regulation Of Neuronal Cell-Type-Specific Transcription By Non-Cg Methylation And Mecp2, James Russell Moore
Regulation Of Neuronal Cell-Type-Specific Transcription By Non-Cg Methylation And Mecp2, James Russell Moore
Arts & Sciences Graduate Student Theses and Dissertations
Modulation of gene expression is fundamental to the exceptional complexity and diversity of cells in the nervous system. Within that last decade, evidence has emerged that neurons utilize unique forms of DNA methylation to regulate transcriptional programs, with multiple types of neurons displaying high levels of cytosine methylation in a non-CG context compared to non-neural cells. This non-CG methylation primarily occurs at CA dinucleotides (mCA) and is read out by methyl-CpG binding protein 2 (MeCP2). Inactivation of MeCP2 results in Rett Syndrome (RTT), a severe neurodevelopmental disorder, while overexpression of MeCP2 results in MeCP2 duplication syndrome, an autism spectrum disorder. …
Identification And Characterization Of Ube3a Gain Of Function Variants As A Driver Of Neurodevelopmental Disease, Kellan Phoebe Weston
Identification And Characterization Of Ube3a Gain Of Function Variants As A Driver Of Neurodevelopmental Disease, Kellan Phoebe Weston
Arts & Sciences Graduate Student Theses and Dissertations
UBE3A is a HECT (homologous to E6AP-Terminus) domain E3 ubiquitin ligase that targets substrate proteins for polyubiquitination and subsequent degradation through the ubiquitin-proteasome pathway. The UBE3A gene is of unique interest for its gene dosage-dependent effect in the developing brain: deletion of the maternal copy of UBE3A causes a severe intellectual disability known as Angelman syndrome; meanwhile, duplication or triplication of the genomic region containing UBE3A is linked to a prevalent syndromic form of autism known as Dup15q syndrome. However, little is known about the effects of missense variants which cause a single amino acid change in the resulting UBE3A …
Investigating The Involvement Of Gabaergic Interneurons And A Gene Therapy Strategy For Epilepsy In Cln2 Disease, Keigo Takahashi
Investigating The Involvement Of Gabaergic Interneurons And A Gene Therapy Strategy For Epilepsy In Cln2 Disease, Keigo Takahashi
Arts & Sciences Graduate Student Theses and Dissertations
The neuronal ceroid lipofuscinoses (NCLs) are a group of neurodegenerative lysosomal storage disorders affecting children and young adults. CLN2 disease, or classic late infantile neuronal ceroid lipofuscinosis, is one of the most common forms of NCL and is caused by a deficiency of tripeptidyl peptidase 1 (TPP1). Although an FDA-approved enzyme replacement therapy for CLN2 disease now exists, a poor understanding of pathophysiology has hampered the development of more effective and persistent therapy. While Cln2R207X/R207X knock-in mice which carry one of the most common pathogenic mutations in human patients were developed in 2017, this genetically accurate mouse model for CLN2 …
Dual Modes Of Dopamine Underly Distinct Facets Of Impulsive Actions, Tzvia Pinkhasov
Dual Modes Of Dopamine Underly Distinct Facets Of Impulsive Actions, Tzvia Pinkhasov
Arts & Sciences Graduate Student Theses and Dissertations
During the pursuit of basic needs, animals sometimes fail to suppress actions that are maladaptive and counterproductive to their survival. In humans, these actions are often called impulsive because they can incur negative consequences. Impulsivity is ubiquitous across psychiatric disorders and related to debilitating outcomes such as substance abuse, crime and suicidality. Despite its risks, a lack of a neural mechanism understanding of impulsive actions impedes the development of effective treatments.In this dissertation, I set out to bridge the knowledge gained from the parallel fields of neuropsychopharmacology, experimental psychology, and systems neuroscience to uncover neural mechanisms of impulsive actions. Clinicians …
Integrating Dna Methylation And 3d-Genome Architecture To Identify Functional Regulatory Sequences In Idh-Mutant Aml, Elisabeth Wilson
Integrating Dna Methylation And 3d-Genome Architecture To Identify Functional Regulatory Sequences In Idh-Mutant Aml, Elisabeth Wilson
Arts & Sciences Graduate Student Theses and Dissertations
Acute myeloid leukemia (AML) is a genetically and phenotypically heterogeneous disease. Recurrent mutations in genes involved in epigenetic pathways are common in AML and are thought to contribute to this variability by disrupting epigenetic patterns relative to normal hematopoietic cells. The most well-studied epigenetic modification in AML is DNA methylation. Although methods for studying DNA methylation have improved significantly in the past decade, the landscape of methylation changes in AML and how they relate to chromatin architecture and gene regulation is still not fully understood. This thesis is focused on the DNA methylation phenotype of IDH1 or IDH2 mutations in …
Neuroepigenetic Mechanisms Of Brain Development: From Technology To Biological Insights, Allen Yen
Neuroepigenetic Mechanisms Of Brain Development: From Technology To Biological Insights, Allen Yen
Arts & Sciences Graduate Student Theses and Dissertations
Each cell in the brain has the same genomic sequence, yet they can have vastly different phenotypes and function. This diversity is a result of complex genetic and signaling pathways, and knowing how these are regulated is key to understanding physiological development and how pathogenic dysfunctions arise. Genomic methods such as chromatin immunoprecipitation followed by sequencing (ChIP-seq) and assay for transposase-accessible chromatin with sequencing (ATAC-seq) have played pivotal roles in dissecting these processes. However, a key limitation is that the cells are destroyed upon observation of their molecular states, which preclude our ability to correlate historical epigenetic information with future …
Understanding Gene Regulation By Non-Cg Dna Methylation And Mecp2 At Cellular Resolution In The Brain, Mati Nemera
Understanding Gene Regulation By Non-Cg Dna Methylation And Mecp2 At Cellular Resolution In The Brain, Mati Nemera
Arts & Sciences Graduate Student Theses and Dissertations
The mammalian brain features a variety of cell types with distinct functions and properties. This cellular diversity is maintained by epigenomic regulation of gene expression. Neurons in particular express long genes and are uniquely enriched for non-CG methylation, especially methylation at CA dinucleotides (mCA). MeCP2, whose mutation results in Rett syndrome, regulates gene expression by binding to mCA. However, the function of this mCA-MeCP2 pathway in the regulation of fine-tuned neuronal gene expression programs has not been investigated. Here, we provide evidence that mCA-MeCP2 pathway plays a role in the maintenance of neuron type-specific gene expression programs at a high …