Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Dicer and Hsp104 function in a negative feedback loop to confer epigenetic robustness

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Schizosaccharomyces pombe

SUBMITTER: Tim Roloff

PROVIDER: E-GEOD-60640 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Dicer and Hsp104 function in a negative feedback loop to confer robustness to environmental stress.

Oberti Daniele D Biasini Adriano A Kirschmann Moritz Alexander MA Genoud Christel C Stunnenberg Rieka R Shimada Yukiko Y Bühler Marc M

Cell reports 20141224 1

Epigenetic mechanisms can be influenced by environmental cues and thus evoke phenotypic variation. This plasticity can be advantageous for adaptation but also detrimental if not tightly controlled. Although having attracted considerable interest, it remains largely unknown if and how environmental cues such as temperature trigger epigenetic alterations. Using fission yeast, we demonstrate that environmentally induced discontinuous phenotypic variation is buffered by a negative feedback loop that ...[more]

PMID: 25543137

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Project description:Cytokines and lineage-specific transcription factors are critical molecular effectors for terminal differentiation during hematopoiesis. Intrinsic transcription factor activity is often believed to drive commitment and differentiation, whereas cytokine receptor signals have been implicated in the regulation of cell proliferation, survival, and differentiation. In erythropoiesis, recent experimental findings provide direct evidence that erythropoietin (Epo) can generate commitment cues via the erythropoietin receptor (EpoR); specifically, EpoR signaling leads to activation of the transcription factor GATA-1, which then triggers transcription of erythrocyte-specific genes. In particular, activated GATA-1 induces two positive feedback loops in the system through the enhanced expression of both inactive GATA-1 and EpoR, the latter of which is externally regulatable by Epo. Based upon this network architecture, we present a mathematical model of GATA-1 activation by EpoR, which bidirectionally links a lineage-specific receptor and transcription factor. Our deterministic model offers insight into stimulus-response relationships between Epo and several downstream effectors. In addition to the survival signals that EpoR provides, steady-state analysis of our model suggests that receptor upregulation during lineage commitment can also generate ultrasensitivity to Epo and bistability in GATA-1 activity. These system-level properties can induce a switch-like characteristic during differentiation and provide robustness to the mature state. The topology also suggests a novel mechanism for achieving robust bistability in a purely deterministic manner without molecular cooperativity. The analytical solution of a generalized, minimal model is provided and the significance of each of the two positive feedback loops is elucidated through bifurcation analysis. This network topology, or variations thereof, may link other receptor-transcription factor pairs and may therefore be of general relevance in cellular decision-making.

Dataset Information

Dicer and Hsp104 function in a negative feedback loop to confer epigenetic robustness

Publications

Dicer and Hsp104 function in a negative feedback loop to confer robustness to environmental stress.

Similar Datasets

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