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"... Now, ... researchers have discovered a molecular timer in mice that plays a role in controlling when they give birth. Surprisingly, the timer is activated in the very first days of pregnancy and operates within the uterus. ...
were studying a protein called KDM6B which regulates gene activity. They suspected that during pregnancy, KDM6B could help regulate the genes involved in the transition to labor.
KDM6B works by removing methyl chemical groups from histones ...
The team noticed that when they blocked KDM6B, pregnancies in the mice became longer, and their babies were born later than usual. ...
But when they carried out detailed analyses on different cell types, they found that KDM6B's effects on pregnancy length were tied to a different cell type called fibroblasts. These structural cells are not typically considered to play a role in the regulation of labor. Moreover, KDM6B regulated these fibroblasts during the first days of pregnancy. ...
Further experiments on mice revealed that shortly after conception, more methyl groups appear on histones near certain genes in uterine fibroblasts. In response, these genes remain inactive, which enables the uterus to support pregnancy.
Over the course of pregnancy, levels of methylation on these histones fade in a slow and steady way, eventually reaching low enough levels that the nearby genes—related to pregnancy events like labor—are activated. This erosion, which does not require KDM6B, functions as a timer. ..."
From the highlights and abstract:
"Highlights
• H3K27me3 levels are adjusted over the uterine fibroblast genome in early pregnancy
• KDM6B deficiency leads to over-accumulation of H3K27me3
• Elevated H3K27me3 is linked to prepartum gene misexpression and delayed labor
• H3K27me3 progressively erodes to induce genes post-midgestation
Summary
Current efforts investigating parturition timing mechanisms have focused on the proximal triggers of labor onset generated in late pregnancy.
By studying the delayed parturition phenotype of mice with uterine fibroblast deficiencies in the histone H3K27me3 demethylase KDM6B, we provide evidence that parturition timing is regulated by events that take place in early pregnancy.
Immediately after copulation, uterine fibroblasts engage in a locus-specific epigenetic program that abruptly adjusts H3K27me3 levels across their genome. In the absence of KDM6B, many of the adjusted loci over-accumulate H3K27me3.
This over-accumulation leads to nearby genes being misexpressed in mid-to-late gestation, a delayed effect partly attributable to a second locus-specific but KDM6B-independent process initiated within uterine fibroblasts soon after implantation.
This second process employs progressive H3K27me3 loss to temporally structure post-midgestational patterns of gene induction. Further dissection of the ways uterine programming controls parturition timing may have relevance to human pregnancy complications such as preterm labor."
What’s Behind Preterm Birth? Scientists Just Found a Big Clue (original press release) "UCSF researchers discovered a molecular timer that gets activated in the first days of pregnancy and influences when mice give birth."
KDM6B-dependent epigenetic programming of uterine fibroblasts in early pregnancy regulates parturition timing in mice (no public access)
Uterine fibroblast cells, in the mouse uterus, shown in red
Graphical abstract
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