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Cooperative assembly confers regulatory specificity and long-term genetic circuit stability [ChIP-Seq]

ABSTRACT: Cooperative assembly confers regulatory specificity and long-term genetic circuit stability [ChIP-Seq]

PROVIDER: PRJNA838835 | ENA |

REPOSITORIES: ENA

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Cooperative assembly confers regulatory specificity and long-term genetic circuit stability

Project description:Cooperative assembly confers regulatory specificity and long-term genetic circuit stability

| PRJNA838831 | ENA

Cooperative assembly confers regulatory specificity and long-term genetic circuit stability [RNA-seq]

Project description:Cooperative assembly confers regulatory specificity and long-term genetic circuit stability [RNA-seq]

| PRJNA838834 | ENA

Cooperative assembly confers regulatory specificity and long-term genetic circuit stability [RNA-seq]

Project description:In eukaryotes, links in gene regulatory networks are often maintained through cooperative self-assembly between transcriptional regulators (TR) and DNA cis-regulatory motifs, a strategy widely thought to enable highly specific regulatory connections to be formed between otherwise weakly-interacting, low-specificity molecular components. Here, we directly test whether this regulatory strategy can be used to engineer regulatory specificity in synthetic gene circuits constructed in yeast. We show that circuits composed of artificial zinc-finger TRs can be effectively insulated from aberrant misregulation of the host cell genome by using cooperative multivalent TR assemblies to program circuit connections. As we demonstrate in experiments and mathematical models, assembly-mediated regulatory connections enable mitigation of circuit-driven fitness defects, resulting in genetic and functional stability of circuits in long-term continuous culture. Our naturally-inspired approach offers a simple, generalizable means for building evolutionarily robust gene circuits that can be scaled to a wide range of host organisms and applications.

2022-05-20 | GSE203145 | GEO

Cooperative assembly confers regulatory specificity and long-term genetic circuit stability [ChIP-Seq]

2022-05-20 | GSE203144 | GEO

Cooperative assembly confers regulatory specificity and long-term genetic circuit stability

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-05-20 | GSE203146 | GEO

Cooperativity, specificity and evolutionary stability of Polycomb targeting in Drosophila

Project description:Cooperativity, specificity and evolutionary stability of Polycomb targeting in Drosophila

| PRJNA258256 | ENA

Circuit design features of a stable two-cell system

Project description:Cell communication within tissues is mediated by multiple paracrine signals including growth factors, which control cell survival and proliferation. Cells and the growth factors they produce and receive constitute a circuit, yet the design features of cell circuits involved in tissue homeostasis are unknown. Here we used computational and experimental approaches to characterize the features of cell circuits based on growth factor exchange between macrophages and fibroblasts, two cell types found in most mammalian tissues. We found that the macrophage-fibroblast cell circuit is stable and robust to perturbations. We employed analytical screening of all possible two-cell circuit topologies and defined the circuit features sufficient for stability, including environmental constraint and negative feedback regulation. Moreover, we discovered that cell-cell contact was essential for the stability of the macrophage-fibroblast circuit. These findings highlight general principles of cell circuit design, and provide a new perspective on quantitative understanding of tissue homeostasis.

2018-02-08 | GSE104511 | GEO

Cooperative adaptation to therapy (CAT) confers resistance in heterogeneous non-small cell lung cancer

Project description:Cooperative adaptation to therapy (CAT) confers resistance in heterogeneous non-small cell lung cancer

| PRJNA530994 | ENA

Disrupting the Myc-Tfeb circuit confers vulnerabilities targeting amino acid homeostasis and provokes metabolic anergy

Project description:Disrupting the Myc-Tfeb circuit confers vulnerabilities targeting amino acid homeostasis and provokes metabolic anergy

| PRJNA643255 | ENA

Cooperative regulation of coupled oncoprotein synthesis and stability in triple-negative breast cancer by EGFR and CDK12/13

Project description:Evidence has long suggested that epidermal growth factor receptor (EGFR) may play a prominent role in triple-negative breast cancer (TNBC) pathogenesis, but clinical trials of EGFR inhibitors have yielded disappointing results. Using a candidate drug screen, we discovered that inhibition of cyclin-dependent kinases 12 and 13 (CDK12/13) dramatically sensitizes diverse models of TNBC to EGFR blockade. This combination therapy drives cell death through the 4E-BP1-dependent suppression of the translation and translation-linked turnover of driver oncoproteins, including MYC. A genome-wide CRISPR/Cas9 screen identified the CCR4-NOT complex as a major determinant of sensitivity to the combination therapy whose loss renders 4E-BP1 unresponsive to drug-induced dephosphorylation, thereby rescuing MYC translational suppression and promoting MYC stability. The central roles of CCR4-NOT and 4E-BP1 in response to the combination therapy were further underscored by the observation of CNOT1 loss and rescue of 4E-BP1 phosphorylation in TNBC cells that naturally evolved therapy resistance. Thus, pharmacological inhibition of CDK12/13 reveals a long proposed EGFR dependence in TNBC that functions through the cooperative regulation of translation-coupled oncoprotein stability.

2023-09-27 | GSE221475 | GEO

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