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Publication : Menin directs regionalized decidual transformation through epigenetically setting PTX3 to balance FGF and BMP signaling.

First Author  Liu M Year  2022
Journal  Nat Commun Volume  13
Issue  1 Pages  1006
PubMed ID  35194044 Mgi Jnum  J:322043
Mgi Id  MGI:7255958 Doi  10.1038/s41467-022-28657-2
Citation  Liu M, et al. (2022) Menin directs regionalized decidual transformation through epigenetically setting PTX3 to balance FGF and BMP signaling. Nat Commun 13(1):1006
abstractText  During decidualization in rodents, uterine stroma undergoes extensive reprograming into distinct cells, forming the discrete regions defined as the primary decidual zone (PDZ), the secondary decidual zone (SDZ) and the layer of undifferentiated stromal cells respectively. Here we show that uterine deletion of Men1, a member of the histone H3K4 methyltransferase complex, disrupts the terminal differentiation of stroma, resulting in chaotic decidualization and pregnancy failure. Genome-wide epigenetic profile reveals that Men1 binding in chromatin recapitulates H3K4me3 distribution. Further transcriptomic investigation demonstrates that Men1 directly regulates the expression of PTX3, an extra-cellular trap for FGF2 in decidual cells. Decreased Ptx3 upon Men1 ablation leads to aberrant activation of ERK1/2 in the SDZ due to the unrestrained FGF2 signal emanated from undifferentiated stromal cells, which blunt BMP2 induction and decidualization. In brief, our study provides genetic and molecular mechanisms for epigenetic rewiring mediated decidual regionalization by Men1 and sheds new light on pregnancy maintenance.
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