The Experts below are selected from a list of 4146 Experts worldwide ranked by ideXlab platform
Leonor Saiz - One of the best experts on this subject based on the ideXlab platform.
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dna looping both enhances and suppreses Transcriptional Noise
Biophysical Journal, 2015Co-Authors: Jose M G Vilar, Leonor SaizAbstract:DNA looping has been observed to enhance and suppress Transcriptional Noise but it is uncertain which of these two opposite effects is to be expected for given conditions. Here, we present the derivation of analytical expressions for the main quantifiers of Transcriptional Noise in terms of the molecular parameters and elucidate the role of DNA looping [1]. Our results rationalize paradoxical experimental observations and provide the first quantitative explanation of landmark individual-cell measurements at the single molecule level on the classical lac operon genetic system [2].[1] Vilar J.M.G. and Saiz L., Physical Review E 89, (6) 062703 (2014).[2] Choi et al., Science 322, 442-446 (2008).
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suppression and enhancement of Transcriptional Noise by dna looping
Physical Review E, 2014Co-Authors: Jose M G Vilar, Leonor SaizAbstract:DNA looping has been observed to enhance and suppress Transcriptional Noise but it is uncertain which of these two opposite effects is to be expected for given conditions. Here, we derive analytical expressions for the main quantifiers of Transcriptional Noise in terms of the molecular parameters and elucidate the role of DNA looping. Our results rationalize paradoxical experimental observations and provide the first quantitative explanation of landmark individual-cell measurements at the single molecule level on the classical lac operon genetic system [Choi, L. Cai, K. Frieda, and X. S. Xie, Science 322, 442 (2008)].
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dna looping in gene regulation from the assembly of macromolecular complexes to the control of Transcriptional Noise
Current Opinion in Genetics & Development, 2005Co-Authors: Jose M G Vilar, Leonor SaizAbstract:The formation of DNA loops by the binding of proteins and protein complexes at distal DNA sites plays a central role in many cellular processes, such as transcription, recombination and replication. Important thermodynamic concepts underlie the assembly of macromolecular complexes on looped DNA. The effects that this process has on the properties of gene regulation extend beyond the traditional view of DNA looping as a mechanism to increase the affinity of regulatory molecules for their cognate sites. Recent developments indicate that DNA looping can also lead to the suppression of cell-to-cell variability, the control of Transcriptional Noise, and the activation of cooperative interactions on demand.
Nigel P Mongan - One of the best experts on this subject based on the ideXlab platform.
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regulation of stem cell pluripotency and differentiation involves a mutual regulatory circuit of the nanog oct4 and sox2 pluripotency transcription factors with polycomb repressive complexes and stem cell micrornas
Stem Cells and Development, 2009Co-Authors: Vasundhra Kashyap, Naira C Rezende, Kymora B Scotland, Sebastian Shaffer, Jenny L Persson, Lorraine J Gudas, Nigel P MonganAbstract:Coordinated transcription factor networks have emerged as the master regulatory mechanisms of stem cell pluripotency and differentiation. Many stem cell-specific transcription factors, including the pluripotency transcription factors, OCT4, NANOG, and SOX2 function in combinatorial complexes to regulate the expression of loci, which are involved in embryonic stem (ES) cell pluripotency and cellular differentiation. This review will address how these pathways form a reciprocal regulatory circuit whereby the equilibrium between stem cell self-renewal, proliferation, and differentiation is in perpetual balance. We will discuss how distinct epigenetic repressive pathways involving polycomb complexes, DNA methylation, and microRNAs cooperate to reduce Transcriptional Noise and to prevent stochastic and aberrant induction of differentiation. We will provide a brief overview of how these networks cooperate to modulate differentiation along hematopoietic and neuronal lineages. Finally, we will describe how aberra...
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regulation of stem cell pluripotency and differentiation involves a mutual regulatory circuit of the nanog oct4 and sox2 pluripotency transcription factors with polycomb repressive complexes and stem cell micrornas
Stem Cells and Development, 2009Co-Authors: Vasundhra Kashyap, Naira C Rezende, Kymora B Scotland, Sebastian Shaffer, Jenny L Persson, Lorraine J Gudas, Nigel P MonganAbstract:Coordinated transcription factor networks have emerged as the master regulatory mechanisms of stem cell pluripotency and differentiation. Many stem cell-specific transcription factors, including the pluripotency transcription factors, OCT4, NANOG, and SOX2 function in combinatorial complexes to regulate the expression of loci, which are involved in embryonic stem (ES) cell pluripotency and cellular differentiation. This review will address how these pathways form a reciprocal regulatory circuit whereby the equilibrium between stem cell self-renewal, proliferation, and differentiation is in perpetual balance. We will discuss how distinct epigenetic repressive pathways involving polycomb complexes, DNA methylation, and microRNAs cooperate to reduce Transcriptional Noise and to prevent stochastic and aberrant induction of differentiation. We will provide a brief overview of how these networks cooperate to modulate differentiation along hematopoietic and neuronal lineages. Finally, we will describe how aberrant functioning of components of the stem cell regulatory network may contribute to malignant transformation of adult stem cells and the establishment of a "cancer stem cell" phenotype and thereby underlie multiple types of human malignancies.
Jose M G Vilar - One of the best experts on this subject based on the ideXlab platform.
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dna looping both enhances and suppreses Transcriptional Noise
Biophysical Journal, 2015Co-Authors: Jose M G Vilar, Leonor SaizAbstract:DNA looping has been observed to enhance and suppress Transcriptional Noise but it is uncertain which of these two opposite effects is to be expected for given conditions. Here, we present the derivation of analytical expressions for the main quantifiers of Transcriptional Noise in terms of the molecular parameters and elucidate the role of DNA looping [1]. Our results rationalize paradoxical experimental observations and provide the first quantitative explanation of landmark individual-cell measurements at the single molecule level on the classical lac operon genetic system [2].[1] Vilar J.M.G. and Saiz L., Physical Review E 89, (6) 062703 (2014).[2] Choi et al., Science 322, 442-446 (2008).
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suppression and enhancement of Transcriptional Noise by dna looping
Physical Review E, 2014Co-Authors: Jose M G Vilar, Leonor SaizAbstract:DNA looping has been observed to enhance and suppress Transcriptional Noise but it is uncertain which of these two opposite effects is to be expected for given conditions. Here, we derive analytical expressions for the main quantifiers of Transcriptional Noise in terms of the molecular parameters and elucidate the role of DNA looping. Our results rationalize paradoxical experimental observations and provide the first quantitative explanation of landmark individual-cell measurements at the single molecule level on the classical lac operon genetic system [Choi, L. Cai, K. Frieda, and X. S. Xie, Science 322, 442 (2008)].
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dna looping in gene regulation from the assembly of macromolecular complexes to the control of Transcriptional Noise
Current Opinion in Genetics & Development, 2005Co-Authors: Jose M G Vilar, Leonor SaizAbstract:The formation of DNA loops by the binding of proteins and protein complexes at distal DNA sites plays a central role in many cellular processes, such as transcription, recombination and replication. Important thermodynamic concepts underlie the assembly of macromolecular complexes on looped DNA. The effects that this process has on the properties of gene regulation extend beyond the traditional view of DNA looping as a mechanism to increase the affinity of regulatory molecules for their cognate sites. Recent developments indicate that DNA looping can also lead to the suppression of cell-to-cell variability, the control of Transcriptional Noise, and the activation of cooperative interactions on demand.
Leor S Weinberger - One of the best experts on this subject based on the ideXlab platform.
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post Transcriptional Noise control
BioEssays, 2019Co-Authors: Maike M K Hansen, Leor S WeinbergerAbstract:Recent evidence indicates that Transcriptional bursts are intrinsically amplified by messenger RNA cytoplasmic processing to generate large stochastic fluctuations in protein levels. These fluctuations can be exploited by cells to enable probabilistic bet-hedging decisions. But large fluctuations in gene expression can also destabilize cell-fate commitment. Thus, it is unclear if cells temporally switch from high to low Noise, and what mechanisms enable this switch. Here, the discovery of a post-Transcriptional mechanism that attenuates Noise in HIV is reviewed. Early in its life cycle, HIV amplifies Transcriptional fluctuations to probabilistically select alternate fates, whereas at late times, HIV utilizes a post-Transcriptional feedback mechanism to commit to a specific fate. Reanalyzing various reported post-Transcriptional negative feedback architectures reveals that they attenuate Noise more efficiently than classic Transcriptional autorepression, leading to the derivation of an assay to detect post-Transcriptional motifs. It is hypothesized that coupling Transcriptional and post-Transcriptional autoregulation enables efficient temporal Noise control to benefit developmental bet-hedging decisions.
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cytoplasmic amplification of Transcriptional Noise generates substantial cell to cell variability
Cell systems, 2018Co-Authors: Maike M K Hansen, Ravi V Desai, Michael L Simpson, Leor S WeinbergerAbstract:Summary Transcription is an episodic process characterized by probabilistic bursts, but how the Transcriptional Noise from these bursts is modulated by cellular physiology remains unclear. Using simulations and single-molecule RNA counting, we examined how cellular processes influence cell-to-cell variability (Noise). The results show that RNA Noise is higher in the cytoplasm than the nucleus in ∼85% of genes across diverse promoters, genomic loci, and cell types (human and mouse). Measurements show further amplification of RNA Noise in the cytoplasm, fitting a model of biphasic mRNA conversion between translation- and degradation-competent states. This multi-state translation-degradation of mRNA also causes substantial Noise amplification in protein levels, ultimately accounting for ∼74% of intrinsic protein variability in cell populations. Overall, the results demonstrate how Noise from Transcriptional bursts is intrinsically amplified by mRNA processing, leading to a large super-Poissonian variability in protein levels.
Vasundhra Kashyap - One of the best experts on this subject based on the ideXlab platform.
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regulation of stem cell pluripotency and differentiation involves a mutual regulatory circuit of the nanog oct4 and sox2 pluripotency transcription factors with polycomb repressive complexes and stem cell micrornas
Stem Cells and Development, 2009Co-Authors: Vasundhra Kashyap, Naira C Rezende, Kymora B Scotland, Sebastian Shaffer, Jenny L Persson, Lorraine J Gudas, Nigel P MonganAbstract:Coordinated transcription factor networks have emerged as the master regulatory mechanisms of stem cell pluripotency and differentiation. Many stem cell-specific transcription factors, including the pluripotency transcription factors, OCT4, NANOG, and SOX2 function in combinatorial complexes to regulate the expression of loci, which are involved in embryonic stem (ES) cell pluripotency and cellular differentiation. This review will address how these pathways form a reciprocal regulatory circuit whereby the equilibrium between stem cell self-renewal, proliferation, and differentiation is in perpetual balance. We will discuss how distinct epigenetic repressive pathways involving polycomb complexes, DNA methylation, and microRNAs cooperate to reduce Transcriptional Noise and to prevent stochastic and aberrant induction of differentiation. We will provide a brief overview of how these networks cooperate to modulate differentiation along hematopoietic and neuronal lineages. Finally, we will describe how aberra...
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regulation of stem cell pluripotency and differentiation involves a mutual regulatory circuit of the nanog oct4 and sox2 pluripotency transcription factors with polycomb repressive complexes and stem cell micrornas
Stem Cells and Development, 2009Co-Authors: Vasundhra Kashyap, Naira C Rezende, Kymora B Scotland, Sebastian Shaffer, Jenny L Persson, Lorraine J Gudas, Nigel P MonganAbstract:Coordinated transcription factor networks have emerged as the master regulatory mechanisms of stem cell pluripotency and differentiation. Many stem cell-specific transcription factors, including the pluripotency transcription factors, OCT4, NANOG, and SOX2 function in combinatorial complexes to regulate the expression of loci, which are involved in embryonic stem (ES) cell pluripotency and cellular differentiation. This review will address how these pathways form a reciprocal regulatory circuit whereby the equilibrium between stem cell self-renewal, proliferation, and differentiation is in perpetual balance. We will discuss how distinct epigenetic repressive pathways involving polycomb complexes, DNA methylation, and microRNAs cooperate to reduce Transcriptional Noise and to prevent stochastic and aberrant induction of differentiation. We will provide a brief overview of how these networks cooperate to modulate differentiation along hematopoietic and neuronal lineages. Finally, we will describe how aberrant functioning of components of the stem cell regulatory network may contribute to malignant transformation of adult stem cells and the establishment of a "cancer stem cell" phenotype and thereby underlie multiple types of human malignancies.
