Forkhead box O member FOXO1 regulates the majority of follicle-stimulating hormone responsive genes in ovarian granulosa cells.
Forkhead box O member FOXO1 regulates the majority of follicle-stimulating hormone responsive genes in ovarian granulosa cells.
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DOI：
10.1016/j.mce.2016.06.020
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发表时间：
2016-10-15
影响因子：
4.1
通讯作者：
Hunzicker-Dunn M
中科院分区：
文献类型：
--
作者：
Herndon MK;Law NC;Donaubauer EM;Kyriss B;Hunzicker-Dunn M
FSH促进卵泡成熟。颗粒细胞（GC）中FSH激活的一条途径是磷脂酰肌醇-3激酶/AKT。据报道，AKT靶点FOXO 1主要作为FSH基因（包括Ccnd 2和Inha）的阻遏物发挥作用。基于其在其他组织中的广泛功能，我们假设FOXO 1可能调控更多的GC基因。我们用空腺病毒或组成型活性FOXO 1转导GC，然后用FSH处理24小时，并进行RNA深度测序。结果表明，FSH调节3，772个基因≥ 2.0倍;这些基因中的60%被FOXO 1激活或抑制。Pathway Studio分析揭示了FOXO 1在代谢、信号传导、运输、发育中抑制的基因的富集，以及FOXO 1在信号传导、细胞骨架功能和凋亡中激活的基因的富集。通过q-PCR（8个基因）和ChIP分析（2个基因）验证基因调控。我们的结论是FOXO 1调节大多数卵泡刺激素的靶基因在GC。
FSH promotes maturation of ovarian follicles. One pathway activated by FSH in granulosa cells (GCs) is phosphatidylinositol-3 kinase/AKT. The AKT target FOXO1 is reported to function primarily as a repressor of FSH genes, including Ccnd2 and Inha. Based on its broad functions in other tissues, we hypothesized that FOXO1 may regulate many more GC genes. We transduced GCs with empty adenovirus or constitutively active FOXO1 followed by treatment with FSH for 24 hours, and conducted RNA deep sequencing. Results show that FSH regulates 3,772 genes ≥ 2.0-fold; 60% of these genes are activated or repressed by FOXO1. Pathway Studio Analysis revealed enrichment of genes repressed by FOXO1 in metabolism, signaling, transport, development, and activated by FOXO1 in signaling, cytoskeletal functions, and apoptosis. Gene regulation was verified by q-PCR (eight genes) and ChIP analysis (two genes). We conclude that FOXO1 regulates the majority of FSH target genes in GCs.