GREBP, a cGMP-response Element-binding Protein Repressing the Transcription of Natriuretic Peptide Receptor 1 (NPR1/GCA)
Bibliographic record
Abstract
NPR1/GCA (natriuretic peptide receptor 1/guanylyl cyclase A) expression is controlled by several agents, including ANP (atrial natriuretic peptide). After ANP stimulation, NPR1/GCA down-regulates the transcriptional activity of its gene via a cGMP-dependent mechanism. Because we previously identified a cis-acting element responsible for this cGMP sensitivity, we proceed here to explore novel putative protein binding to cGMP-response element (cGMP-RE). Using the yeast one-hybrid technique with a human kidney cDNA library, we identified a strong positive clone able to bind cGMP-RE. The clone was derived from 1083-bp-long cDNA of a gene of yet unknown function localized on human chromosome 1 (1p33.36). We named this new protein GREBP (for cGMP-response element-binding protein). DNA binding assays showed 18-fold higher cGMP-RE binding capacity than the controls, whereas an electromobility shift assay indicated a specific binding for the cGMP-RE, and chromatin immunoprecipitation confirmed the binding of GREBP to the element under physiological conditions. By acting on cGMP-RE, GREBP inhibited the expression of a luciferase-coupled NPR1 promoter construct. In H295R cells, ANP heightened GREBP expression by 60% after just 3 h of treatment while inhibiting NPR1/GCA expression by 30%. Silencing GREBP with specific small interfering RNA increased the activity of the luciferase-coupled NPR1 promoter and GCA/NPR1 mRNA levels. GREBP is a nuclear protein mainly expressed in the heart. We report here the existence of a human-specific gene that acts as a transcriptional repressor of the NPR1/GCA gene. NPR1/GCA (natriuretic peptide receptor 1/guanylyl cyclase A) expression is controlled by several agents, including ANP (atrial natriuretic peptide). After ANP stimulation, NPR1/GCA down-regulates the transcriptional activity of its gene via a cGMP-dependent mechanism. Because we previously identified a cis-acting element responsible for this cGMP sensitivity, we proceed here to explore novel putative protein binding to cGMP-response element (cGMP-RE). Using the yeast one-hybrid technique with a human kidney cDNA library, we identified a strong positive clone able to bind cGMP-RE. The clone was derived from 1083-bp-long cDNA of a gene of yet unknown function localized on human chromosome 1 (1p33.36). We named this new protein GREBP (for cGMP-response element-binding protein). DNA binding assays showed 18-fold higher cGMP-RE binding capacity than the controls, whereas an electromobility shift assay indicated a specific binding for the cGMP-RE, and chromatin immunoprecipitation confirmed the binding of GREBP to the element under physiological conditions. By acting on cGMP-RE, GREBP inhibited the expression of a luciferase-coupled NPR1 promoter construct. In H295R cells, ANP heightened GREBP expression by 60% after just 3 h of treatment while inhibiting NPR1/GCA expression by 30%. Silencing GREBP with specific small interfering RNA increased the activity of the luciferase-coupled NPR1 promoter and GCA/NPR1 mRNA levels. GREBP is a nuclear protein mainly expressed in the heart. We report here the existence of a human-specific gene that acts as a transcriptional repressor of the NPR1/GCA gene.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".