Menin directs regionalized decidual transformation through epigenetically setting PTX3 to balance FGF and BMP signaling.
Menin directs regionalized decidual transformation through epigenetically setting PTX3 to balance FGF and BMP signaling.
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DOI：
10.1038/s41467-022-28657-2
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发表时间：
2022-02-22
影响因子：
16.6
通讯作者：
Kong S
中科院分区：
文献类型：
--
作者：
Liu M;Deng W;Tang L;Liu M;Bao H;Guo C;Zhang C;Lu J;Wang H;Lu Z;Kong S
在啮齿动物的蜕膜化过程中，子宫基质经历广泛的重编程成不同的细胞，形成分别被定义为初级蜕膜区（PDZ）、次级蜕膜区（SDZ）和未分化基质细胞层的离散区域。在这里，我们表明，子宫删除Men 1，组蛋白H3 K4甲基转移酶复合物的成员，破坏了基质的终末分化，导致混乱的蜕膜化和妊娠失败。全基因组表观遗传图谱显示Men 1在染色质中的结合概括了H3 K4 me 3的分布。进一步的转录组学研究表明，Men 1直接调节PTX 3的表达，PTX 3是蜕膜细胞中FGF 2的细胞外陷阱。Men 1消融后Ptx 3的减少导致SDZ中ERK 1/2的异常激活，这是由于未分化的基质细胞发出的无限制的FGF 2信号，其钝化BMP 2诱导和蜕膜化。简而言之，我们的研究为Men 1介导的表观遗传重布线介导的蜕膜区域化提供了遗传和分子机制，并为妊娠维持提供了新的见解。子宫内膜间质的蜕膜化是维持妊娠的关键。在这里，作者揭示了Menin通过H3 K4 me 3修饰确保PTX 3的表达，以平衡正常妊娠蜕膜中的BMP和FGF信号。
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. The decidualization of endometrial stroma is critical for pregnancy maintenance. Here the authors reveal that Menin ensures the expression of PTX3 through H3K4me3 modification, to balance the BMP and FGF signal in the decidua for normal pregnancy.
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DOI：
10.1242/dev.037689
发表时间：
2010-11
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Dorey K;Amaya E
通讯作者：
Amaya E
DOI：
10.1530/rep-15-0107
发表时间：
2015-06
期刊：
Reproduction (Cambridge, England)
影响因子：
--
作者：
Alam SM;Konno T;Soares MJ
通讯作者：
Soares MJ
影响因子：
7.3
作者：
Gaynor LM;Colucci F
通讯作者：
Colucci F
影响因子：
82.9
作者：
Cha J;Sun X;Dey SK
通讯作者：
Dey SK
影响因子：
16.6
作者：
Kuwahara, Makoto;Suzuki, Junpei;Tofukuji, Soichi;Yamada, Takeshi;Kanoh, Makoto;Matsumoto, Akira;Maruyama, Saho;Kometani, Kohei;Kurosaki, Tomohiro;Ohara, Osamu;Nakayama, Toshinori;Yamashita, Masakatsu
通讯作者：
Yamashita, Masakatsu