Transposon-mediated rewiring of gene regulatory networks contributed to the evolution of pregnancy in mammals
Transposon-mediated rewiring of gene regulatory networks contributed to the evolution of pregnancy in mammals
复制标题
DOI：
10.1038/ng.917
复制
发表时间：
2011-11-01
期刊：
影响因子：
30.8
通讯作者：
Wagner, Guenter P.
中科院分区：
文献类型：
--
作者：
Lynch, Vincent J.;Leclerc, Robert D.;Wagner, Guenter P.
生物学中的一个基本挑战是解释新的表型特征的起源，如新的细胞类型（1-4）;产生新奇的分子机制尚不清楚（5-7）。我们使用比较RNA-Seq探索了哺乳动物子宫内膜细胞的基因调控景观，发现1，532个基因被招募到胎盘哺乳动物的子宫内膜表达中，表明妊娠的进化与基因调控网络的大规模重新布线有关。约13%的募集基因在真兽目特异性转座因子（MER 20）的200 kb内。这些转座子具有增强子、绝缘子和阻遏子的表观遗传特征，直接结合妊娠必需的转录因子，并响应孕酮和cAMP协调调节基因表达。我们的结论是，转座因子，MER 20，有助于起源的一种新的基因调控网络，致力于怀孕的胎盘哺乳动物，特别是通过招募到子宫内膜间质细胞的cAMP信号通路。
A fundamental challenge in biology is explaining the origin of novel phenotypic characters such as new cell types(1-4); the molecular mechanisms that give rise to novelties are unclear(5-7). We explored the gene regulatory landscape of mammalian endometrial cells using comparative RNA-Seq and found that 1,532 genes were recruited into endometrial expression in placental mammals, indicating that the evolution of pregnancy was associated with a large-scale rewiring of the gene regulatory network. About 13% of recruited genes are within 200 kb of a Eutherian-specific transposable element (MER20). These transposons have the epigenetic signatures of enhancers, insulators and repressors, directly bind transcription factors essential for pregnancy and coordinately regulate gene expression in response to progesterone and cAMP. We conclude that the transposable element, MER20, contributed to the origin of a novel gene regulatory network dedicated to pregnancy in placental mammals, particularly by recruiting the cAMP signaling pathway into endometrial stromal cells.