JUND plays a genome-wide role in the quiescent to contractile switch in the pregnant human myometrium
Bibliographic record
Abstract
Abstract The myometrium, the muscular layer of the uterus, undergoes crucial transitions during pregnancy, maintaining quiescence throughout gestation, and generating coordinated contractions during labor. Dysregulation of this transition can lead to premature labor with serious complications for the infant. Despite extensive gene expression data available for varying myometrial states, the molecular mechanisms governing the increase in contraction- associated gene expression at labor onset remain unclear. Transcription factors, such as JUND and progesterone receptor (PR), play essential roles in regulating transcription of select myometrial contraction-associated genes, however, a broader understanding of their involvement in transcriptional regulation at a genome-wide scale is lacking. This study examines changes in transcription and JUND binding within human myometrial tissue during the transition from quiescence (term-not-in labor/TNIL) to contractility (term labor/TL). Total RNA- sequencing reveals a global increase in primary transcript levels at TL, with AP-1/JUND binding motifs overrepresented in the promoters of upregulated transcripts. Interestingly, ChIP-seq analysis demonstrates higher JUND enrichment in TNIL compared to TL tissues, suggesting its role in preparing the myometrium for labor onset. Integration of JUND and PR ChIP-seq data identifies over 10,000 gene promoters bound by both factors at TNIL and TL, including genes involved in labor-driving processes. Additionally, the study uncovers elevated levels of enhancer RNAs (eRNAs) at intergenic JUND peaks in laboring myometrial tissues, and implicates additional transcription factors, such as NFKB and ETS, in the regulatory switch from quiescence to contractility. In summary, this research enhances our understanding of the myometrial molecular regulatory network during pregnancy and labor, shedding light on the roles of JUND and PR in gene expression regulation genome-wide. These findings open avenues for further exploration, potentially leading to improved interventions for preventing premature labor and the associated complications.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 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".