Forkhead box O member FOXO1 regulates the majority of follicle-stimulating hormone responsive genes in ovarian granulosa cells.
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 h, and conducted RNA deep sequencing. Results show that FSH regulates 3772 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.
School of Molecular Biosciences and the Center for Reproductive Biology, Washington State University, Pullman WA 99163, USA. Electronic address: mkmeyer@vetmed.wsu.edu.
Maria K
MK
Herndon
School of Molecular Biosciences and the Center for Reproductive Biology, Washington State University, Pullman WA 99163, USA. Electronic address: nathan_law@vetmed.wsu.edu.
Nathan C
NC
Law
School of Molecular Biosciences and the Center for Reproductive Biology, Washington State University, Pullman WA 99163, USA. Electronic address: edonaubauer@vetmed.wsu.edu.
Elyse M
EM
Donaubauer
School of Molecular Biosciences and the Center for Reproductive Biology, Washington State University, Pullman WA 99163, USA. Electronic address: kyrissbp@gmail.com.
Brandon
B
Kyriss
School of Molecular Biosciences and the Center for Reproductive Biology, Washington State University, Pullman WA 99163, USA. Electronic address: mehd@wsu.edu.
Mary
M
Hunzicker-Dunn
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects*; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017423:Sequence Analysis, RNA / Q000379:methods; D000071161:Forkhead Box Protein O1
D005640:Follicle Stimulating Hormone; D009419:Nerve Tissue Proteins; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1
FOXO1; Follicle-stimulating hormone; Granulosa cells; RNA deep sequencing