scholarly journals Identification of a post-transcriptional regulatory element that responds to glucose in the African trypanosome

2018 ◽  
Author(s):  
Yijian Qiu ◽  
Vijay Shankar ◽  
Rooksana E. Noorai ◽  
Nelson Yeung ◽  
Sarah Grace McAlpine ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nutrient Availability ◽  
Regulatory Element ◽  
Regulation Of Gene Expression ◽  
Blood Stage ◽  
Stem Loop ◽  
Dynamic Regulation ◽  
African Trypanosome ◽  
Atp Production ◽  
Altered Glucose

ABSTRACTThe ability to adapt to varying nutrient availability in changing environments is critical for successful parasitism. The lifecycle stages of the African trypanosome, Trypanosoma brucei, that infect the host mammalian bloodstream utilize glucose exclusively for ATP production. The finding that trypanosomes also inhabit other tissues that frequently contain lower glucose concentrations suggests blood stage parasites may have to respond to a dynamic environment with changing nutrient availability in order to survive. However, little is known about how the parasites coordinate gene expression with nutrient availability. Through transcriptome analysis, we have found blood stage parasites deprived of glucose alter gene expression in a pattern similar to transcriptome changes triggered by other stresses. A surprisingly low concentration of glucose (<10 μM) was required to initiate the response. To further understand the dynamic regulation of gene expression that occurs in response to altered glucose availability in the environment, we have interrogated the 3’UTR of cytochrome c oxidase subunit VI, a known lifecycle stage regulated gene, and have identified a stem-loop structure that confers glucose-responsive regulation at the translational level.

scholarly journals Sophisticated Conversations between Chromatin and Chromatin Remodelers, and Dissonances in Cancer

2021 ◽  
Vol 22 (11) ◽  
pp. 5578
Author(s):  
Cedric R. Clapier
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Structural Diversity ◽  
Nucleosome Positioning ◽  
Basic Mechanism ◽  
Progressive Increase ◽  
Chromatin Organization ◽  
Dna Translocation ◽  
Dynamic Regulation ◽  
Cooperative Action

The establishment and maintenance of genome packaging into chromatin contribute to define specific cellular identity and function. Dynamic regulation of chromatin organization and nucleosome positioning are critical to all DNA transactions—in particular, the regulation of gene expression—and involve the cooperative action of sequence-specific DNA-binding factors, histone modifying enzymes, and remodelers. Remodelers are molecular machines that generate various chromatin landscapes, adjust nucleosome positioning, and alter DNA accessibility by using ATP binding and hydrolysis to perform DNA translocation, which is highly regulated through sophisticated structural and functional conversations with nucleosomes. In this review, I first present the functional and structural diversity of remodelers, while emphasizing the basic mechanism of DNA translocation, the common regulatory aspects, and the hand-in-hand progressive increase in complexity of the regulatory conversations between remodelers and nucleosomes that accompanies the increase in challenges of remodeling processes. Next, I examine how, through nucleosome positioning, remodelers guide the regulation of gene expression. Finally, I explore various aspects of how alterations/mutations in remodelers introduce dissonance into the conversations between remodelers and nucleosomes, modify chromatin organization, and contribute to oncogenesis.

Chromatin-Modifying Enzymes in T Cell Development

2020 ◽  
Vol 38 (1) ◽  
pp. 397-419
Author(s):  
Michael J. Shapiro ◽  
Virginia Smith Shapiro
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Biological Effects ◽  
Critical Role ◽  
T Cell Development ◽  
Regulation Of Gene Expression ◽  
Chromatin Accessibility ◽  
Cell Development ◽  
Specific Gene ◽  
Dynamic Regulation

T cell development involves stepwise progression through defined stages that give rise to multiple T cell subtypes, and this is accompanied by the establishment of stage-specific gene expression. Changes in chromatin accessibility and chromatin modifications accompany changes in gene expression during T cell development. Chromatin-modifying enzymes that add or reverse covalent modifications to DNA and histones have a critical role in the dynamic regulation of gene expression throughout T cell development. As each chromatin-modifying enzyme has multiple family members that are typically all coexpressed during T cell development, their function is sometimes revealed only when two related enzymes are concurrently deleted. This work has also revealed that the biological effects of these enzymes often involve regulation of a limited set of targets. The growing diversity in the types and sites of modification, as well as the potential for a single enzyme to catalyze multiple modifications, is also highlighted.

scholarly journals Antigene-block strategy: Effective regulation of gene expression by 2′,4′-BNA-modified TFOs with an additional stem-loop structure

2005 ◽  
Vol 49 (1) ◽  
pp. 335-336 ◽  
Author(s):  
Naoto Tsuda ◽  
Ayumi Matsumoto ◽  
Aya Ito ◽  
Tomomi Uneda ◽  
Atsuhiro Tanabe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Loop Structure ◽  
Stem Loop ◽  
Stem Loop Structure

scholarly journals Identification of a transcriptional signature found in multiple models of ASD and related disorders

2022 ◽  
Author(s):  
Samuel Thudium ◽  
Katherine C Palozola ◽  
Eloise L'Her ◽  
Erica Korb
Keyword(s):  
Gene Expression ◽  
Epigenetic Regulation ◽  
Neurodevelopmental Disorders ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Autism Spectrum ◽  
Cellular Mechanisms ◽  
Dynamic Regulation ◽  
Transcriptional Signature ◽  
Chromatin Modifiers

Epigenetic regulation plays a critical role in many neurodevelopmental disorders, including Autism Spectrum Disorder (ASD). In particular, many such disorders are the result of mutations in genes that encode chromatin modifying proteins. However, while these disorders share many features, it is unclear whether they also share gene expression disruptions resulting from the aberrant regulation of chromatin. We examined 5 chromatin modifiers that are all linked to ASD despite their different roles in regulating chromatin. Specifically, we depleted Ash1L, Chd8, Crebbp, Ehmt1, and Nsd1 in parallel in a highly controlled neuronal culture system. We then identified sets of shared genes, or transcriptional signatures, that are differentially expressed following loss of multiple ASD-linked chromatin modifiers. We examined the functions of genes within the transcriptional signatures and found an enrichment in many neurotransmitter transport genes and activity-dependent genes. In addition, these genes are enriched for specific chromatin features such as bivalent domains that allow for highly dynamic regulation of gene expression. The downregulated transcriptional signature is also observed within multiple mouse models of neurodevelopmental disorders that result in ASD, but not those only associated with intellectual disability. Finally, the downregulated transcriptional signature can distinguish between neurons generated from iPSCs derived from healthy donors and idiopathic ASD patients through RNA-deconvolution, demonstrating that this gene set is relevant to the human disorder. This work identifies a transcriptional signature that is found within many neurodevelopmental syndromes, helping to elucidate the link between epigenetic regulation and the underlying cellular mechanisms that result in ASD.

scholarly journals Heat-triggered remote control of CRISPR-dCas9 for tunable transcriptional modulation

2019 ◽  
Author(s):  
Lena Gamboa ◽  
Erick V. Phung ◽  
Haoxin Li ◽  
Jared P. Meyers ◽  
Gabriel A. Kwong
Keyword(s):  
Gene Expression ◽  
Remote Control ◽  
Mammalian Cell ◽  
Regulation Of Gene Expression ◽  
Dynamic Regulation ◽  
Short Pulses ◽  
Cell Functions ◽  
New Approaches ◽  
Gene Switches ◽  
Transcriptional Modulation

ABSTRACTEmerging CRISPR technologies are enabling powerful new approaches to control mammalian cell functions, yet the lack of spatially-defined, noninvasive modalities to direct their function limit their potential as biological tools and pose a major challenge for clinical translation. Here we confer remote control of CRISPR-dCas9 activity using thermal gene switches, enabling the dynamic regulation of gene expression using short pulses of heat to modulate transcriptional commands.

scholarly journals A unique palindromic element mediates gamma interferon induction of mig gene expression.

1994 ◽  
Vol 14 (2) ◽  
pp. 914-922 ◽  
Author(s):  
P Wong ◽  
C W Severns ◽  
N B Guyer ◽  
T M Wright
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Regulatory Element ◽  
Regulation Of Gene Expression ◽  
Gamma Interferon ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Monocytic Cell ◽  
Platelet Factor ◽  
Ifn Gamma

To define the molecular mechanisms involved in the action of gamma interferon (IFN-gamma), we have analyzed the transcriptional regulation of the mig (monokine induced by gamma interferon) gene, a member of the platelet factor 4-interleukin-8 cytokine family that is expressed in murine macrophages specifically in response to IFN-gamma. Analysis of mig/CAT chimeric constructs transiently transfected into the RAW 264.7 mouse monocytic cell line revealed a unique IFN-gamma-responsive element (gamma RE-1). The sequence of this cis regulatory element defined by deletion analysis contains an imperfect inverted repeat extending 27 bp. Examination of mig/CAT constructs with mutations in gamma RE-1 revealed that the palindromic positions in the element were essential for activity. Consistent with its function as an enhancer, a single copy of gamma RE-1 conferred IFN-gamma inducibility to a heterologous (herpes simplex virus thymidine kinase) promoter. Exonuclease III protection assays demonstrated symmetrical protection of a mig promoter fragment centered about the gamma RE-1 palindromic sequence. Using the gel electrophoretic mobility shift assay, we identified a factor (gamma RF-1) present in nuclear extracts prepared from IFN-gamma-stimulated RAW 264.7 cells which binds to gamma RE-1. The activation of gamma RF-1 occurred rapidly (within 1 min) in response to IFN-gamma and was independent of protein synthesis. Similar to the expression of mig mRNA, the formation of gamma RF-1 was selectively induced by IFN-gamma and not IFN-alpha. The regulation of gene expression through gamma RF-1 and gamma RE-1 may explain the preferential activation of a subset of interferon-inducible genes by IFN-gamma.

scholarly journals Epigenomic profiling of primate lymphoblastoid cell lines reveals the evolutionary patterns of epigenetic activities in gene regulatory architectures

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Raquel García-Pérez ◽  
Paula Esteller-Cucala ◽  
Glòria Mas ◽  
Irene Lobón ◽  
Valerio Di Carlo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Regulatory Element ◽  
Regulation Of Gene Expression ◽  
Regulatory Elements ◽  
Lymphoblastoid Cell Lines ◽  
Whole Genome ◽  
Specific Expression ◽  
Gene Regulatory ◽  
Human Specific

AbstractChanges in the epigenetic regulation of gene expression have a central role in evolution. Here, we extensively profiled a panel of human, chimpanzee, gorilla, orangutan, and macaque lymphoblastoid cell lines (LCLs), using ChIP-seq for five histone marks, ATAC-seq and RNA-seq, further complemented with whole genome sequencing (WGS) and whole genome bisulfite sequencing (WGBS). We annotated regulatory elements (RE) and integrated chromatin contact maps to define gene regulatory architectures, creating the largest catalog of RE in primates to date. We report that epigenetic conservation and its correlation with sequence conservation in primates depends on the activity state of the regulatory element. Our gene regulatory architectures reveal the coordination of different types of components and highlight the role of promoters and intragenic enhancers (gE) in the regulation of gene expression. We observe that most regulatory changes occur in weakly active gE. Remarkably, novel human-specific gE with weak activities are enriched in human-specific nucleotide changes. These elements appear in genes with signals of positive selection and human acceleration, tissue-specific expression, and particular functional enrichments, suggesting that the regulatory evolution of these genes may have contributed to human adaptation.

scholarly journals KDM6 Demethylases and Their Roles in Human Cancers

2021 ◽  
Vol 11 ◽  
Author(s):  
Chunyan Hua ◽  
Jiaqing Chen ◽  
Shuting Li ◽  
Jianan Zhou ◽  
Jiahong Fu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Microenvironment ◽  
Regulation Of Gene Expression ◽  
Coordinated Control ◽  
Structural Features ◽  
Dependent Manner ◽  
Histone Demethylation ◽  
Dynamic Regulation ◽  
Human Cancers ◽  
Prevention And Treatment

Cancer therapy is moving beyond traditional chemotherapy to include epigenetic approaches. KDM6 demethylases are dynamic regulation of gene expression by histone demethylation in response to diverse stimuli, and thus their dysregulation has been observed in various cancers. In this review, we first briefly introduce structural features of KDM6 subfamily, and then discuss the regulation of KDM6, which involves the coordinated control between cellular metabolism (intrinsic regulators) and tumor microenvironment (extrinsic stimuli). We further describe the aberrant functions of KDM6 in human cancers, acting as either a tumor suppressor or an oncoprotein in a context-dependent manner. Finally, we propose potential therapy of KDM6 enzymes based on their structural features, epigenetics, and immunomodulatory mechanisms, providing novel insights for prevention and treatment of cancers.

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