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Full-Text Articles in Molecular Biology

A Gene-Centered C. Elegans Protein-Dna Interaction Network Provides A Framework For Functional Predictions, Juan Fuxman Bass, Carles Pons, Lucie Kozlowski, John S. Reece-Hoyes, Shaleen Shrestha, Amy D. Holdorf, Akihiro Mori, Chad L. Myers, Albertha J. M. Walhout Oct 2016

A Gene-Centered C. Elegans Protein-Dna Interaction Network Provides A Framework For Functional Predictions, Juan Fuxman Bass, Carles Pons, Lucie Kozlowski, John S. Reece-Hoyes, Shaleen Shrestha, Amy D. Holdorf, Akihiro Mori, Chad L. Myers, Albertha J. M. Walhout

Open Access Articles

Transcription factors (TFs) play a central role in controlling spatiotemporal gene expression and the response to environmental cues. A comprehensive understanding of gene regulation requires integrating physical protein-DNA interactions (PDIs) with TF regulatory activity, expression patterns, and phenotypic data. Although great progress has been made in mapping PDIs using chromatin immunoprecipitation, these studies have only characterized ~10% of TFs in any metazoan species. The nematode C. elegans has been widely used to study gene regulation due to its compact genome with short regulatory sequences. Here, we delineated the largest gene-centered metazoan PDI network to date by examining interactions between 90 ...


Reactive Oxygen Species-Mediated Neurodegeneration Is Independent Of The Ryanodine Receptor In Caenorhabditis Elegans, Lyndsay E.A. Young, Daniel C. Williams Oct 2015

Reactive Oxygen Species-Mediated Neurodegeneration Is Independent Of The Ryanodine Receptor In Caenorhabditis Elegans, Lyndsay E.A. Young, Daniel C. Williams

Journal of the South Carolina Academy of Science

Despite the significant impacts on human health caused by neurodegeneration, our understanding of the degeneration process is incomplete. The nematode Caenorhabditis elegans is emerging as a genetic model organism well suited for identification of conserved cellular mechanisms and molecular pathways of neurodegeneration. Studies in the worm have identified factors that contribute to neurodegeneration, including excitotoxicity and stress due to reactive oxygen species (ROS). Disruption of the gene unc-68, which encodes the ryanodine receptor, abolishes excitotoxic cell death, indicating a role for calcium (Ca2+) signaling in neurodegeneration. We tested the requirement for unc-68 in ROS-mediated neurodegeneration using the genetically encoded ...


Mirnas Collaborate With A Conserved Rna Binding Protein To Ensure Development And Stress Response In C. Elegans, Rebecca A. Zabinsky Jan 2015

Mirnas Collaborate With A Conserved Rna Binding Protein To Ensure Development And Stress Response In C. Elegans, Rebecca A. Zabinsky

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

miRNAs play critical roles in development and other cellular processes in C. elegans even though most individual miRNAs are not essential for development or viability (Miska et al., 2007). Extensive studies in the field have suggested that most miRNA functions are executed through complex miRNA-target interaction networks. Furthermore, such networks may also function semi-redundantly with other regulatory systems to shape gene expression dynamics for proper physiological functions. Hypothesizing that miRNAs function in stress conditions, I collaborated with a postdoctoral fellow to investigate the role of a specific miRNA miR-71 in starvation induced L1 diapause. Hypothesizing that miRNAs collaborate with other ...


Regulation Of C. Elegans Developmental Timing By The Gata Transcription Factor Elt-1, Max Louis Cohen Jan 2013

Regulation Of C. Elegans Developmental Timing By The Gata Transcription Factor Elt-1, Max Louis Cohen

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The heterochronic gene network controls developmental timing in the nematode roundworm Caenorhabditis elegans. Bi-stable switch-like changes in gene expression occur during its development as stage-specific microRNAs are expressed and subsequently down-regulate other stage-specific factors, allowing for developmental progression. Key genes in this regulatory network are phylogenetically conserved and include the post-transcriptional microRNA repressor lin-28; the nuclear hormone receptor daf-12; and the microRNAs lin-4, mir-48, mir-84, mir-241, and let-7. daf-12 is the only factor currently known to regulate transcription of the Let-7 microRNA family, but its contribution is insufficient to account for all of the transcriptional regulation observed. In this work ...


Sirt1 Regulation Of The Heat Shock Response In An Hsf1-Dependent Manner And The Impact Of Caloric Restriction, Rachel Rene Raynes Jan 2013

Sirt1 Regulation Of The Heat Shock Response In An Hsf1-Dependent Manner And The Impact Of Caloric Restriction, Rachel Rene Raynes

Graduate Theses and Dissertations

The heat shock response (HSR) is the cell's molecular reaction to protein damaging stress and is critical in the management of denatured proteins. Activation of HSF1, the master transcriptional regulator of the HSR, results in the induction of molecular chaperones called heat shock proteins (HSPs). Transcription of hsp genes is promoted by the hyperphosphorylation of HSF1, while the attenuation of the HSR is regulated by a dual mechanism involving negative feedback inhibition from HSPs and acetylation at a critical lysine residue within the DNA binding domain of HSF1, which results in a loss of affinity for DNA. SIRT1 is ...


Regulation And Dynamic Behavior Of The Heat Shock Transcription Factor Hsf-1 In C. Elegans, Elizabeth A. Morton Jan 2013

Regulation And Dynamic Behavior Of The Heat Shock Transcription Factor Hsf-1 In C. Elegans, Elizabeth A. Morton

Publicly Accessible Penn Dissertations

Eukaryotic cells respond to heat stress by activating the transcription factor HSF1. In addition to its role in stress response, HSF1 also functions in protein homeostasis, aging, innate immunity, and cancer. Despite prominent HSF1 involvement in processes pertinent to human health and disease, there are still gaps in our understanding of HSF1. For example, controversy exists regarding the localization of HSF1, the identity of HSF1 regulators, and the function and conservation of heat-induced HSF1 stress granules. Many of the physiological roles for HSF1 have been defined using the model organism Caenorhabditis elegans, yet little is known about how the molecular ...