Centrala begrepp
The human myometrium undergoes extensive epigenomic and transcriptomic remodeling during pregnancy to prepare for parturition, which is critical for understanding the molecular mechanisms underlying myometrial quiescence and contractility.
Sammanfattning
The study investigated the epigenomic landscape and transcriptome of human term pregnant, non-labor myometrial tissues to understand the gene regulatory mechanisms that maintain myometrial quiescence and prepare the uterus for parturition.
Key highlights:
- Identified over 30,000 putative enhancers marked by H3K27ac and H3K4me1 in the myometrium, with enrichment of binding motifs for known myometrial regulators like AP-1, STAT, NFκB, and PGR.
- Detected 540 putative super enhancers, 76% of which co-localized with PGR binding sites and were associated with highly expressed genes involved in myometrial function.
- Functionally screened a 35-kb upstream region of the contractile-suppressing gene PLCL2 and identified it as a cis-acting element regulated by the progesterone receptor (PGR).
- Demonstrated that PGR overexpression can increase PLCL2 expression in myometrial cells, and the inferred PGR activity positively correlates with PLCL2 mRNA levels in human myometrial specimens.
These findings provide a comprehensive resource to study gene regulatory mechanisms in the human myometrium and identify PGR as a key regulator of the contractile machinery, which could inform the development of novel interventions for parturition disorders like preterm birth.
Statistik
The myometrium contains an average of 44,238 H3K27ac-positive and 74,325 H3K4me1-positive genomic regions.
The myometrium expresses an average of 12,157 active genes (FPKM ≥ 1).
A total of 27,162 chromatin loops were identified in the myometrium.
Citat
"Results of this study serve as a resource to study gene regulatory mechanisms in the human myometrium at the term pregnancy stage for further advancing women's health research."
"These findings build upon our understanding of myometrial remodeling throughout gestation and will be pertinent for the development of medical interventions aiming to address pre-term birth."