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 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 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 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 TIS11 Family Proteins and Their Roles in Posttranscriptional Gene Regulation

2009 ◽  
Vol 2009 ◽  
pp. 1-11 ◽  
Author(s):  
Maria Baou ◽  
Andrew Jewell ◽  
John J. Murphy
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Posttranscriptional Regulation ◽  
Regulation Of Gene Expression ◽  
Present Review ◽  
Untranslated Regions ◽  
Cell Functions ◽  
Small Family ◽  
The Past ◽  
Posttranscriptional Gene Regulation

Posttranscriptional regulation of gene expression of mRNAs containing adenine-uridine rich elements (AREs) in their untranslated regions is mediated by a number of different proteins that interact with these elements to either stabilise or destabilise them. The present review concerns the TPA-inducible sequence 11 (TIS11) protein family, a small family of proteins, that appears to interact with ARE-containing mRNAs and promote their degradation. This family of proteins has been extensively studied in the past decade. Studies have focussed on determining their biochemical functions, identifying their target mRNAs, and determining their roles in cell functions and diseases.

scholarly journals Dynamic mRNP Remodeling in Response to Internal and External Stimuli

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1310 ◽  
Author(s):  
Kathi Zarnack ◽  
Sureshkumar Balasubramanian ◽  
Michael P. Gantier ◽  
Vladislav Kunetsky ◽  
Michael Kracht ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Rna Binding ◽  
Environmental Changes ◽  
Rna Binding Proteins ◽  
Regulation Of Gene Expression ◽  
Cellular Processes ◽  
Messenger Ribonucleoprotein ◽  
Transcriptional Modulation ◽  
External Stimuli

Signal transduction and the regulation of gene expression are fundamental processes in every cell. RNA-binding proteins (RBPs) play a key role in the post-transcriptional modulation of gene expression in response to both internal and external stimuli. However, how signaling pathways regulate the assembly of RBPs with mRNAs remains largely unknown. Here, we summarize observations showing that the formation and composition of messenger ribonucleoprotein particles (mRNPs) is dynamically remodeled in space and time by specific signaling cascades and the resulting post-translational modifications. The integration of signaling events with gene expression is key to the rapid adaptation of cells to environmental changes and stress. Only a combined approach analyzing the signal transduction pathways and the changes in post-transcriptional gene expression they cause will unravel the mechanisms coordinating these important cellular processes.

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