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CBP-CITED4 is required for luteinizing hormone-triggered target gene expression during ovulation
Yin-Li Zhang1, Yan Xia1, Chao Yu1
1Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, China.
Molecular Human Reproduction
|June 1, 2014
Summary
Luteinizing hormone (LH) triggers ovulation via the ERK1/2 pathway. This study identifies CITED4 as a key LH target gene that, along with histone acetylation, is crucial for ovulation.
Area of Science:
- Reproductive biology
- Molecular endocrinology
- Gene regulation
Background:
- Luteinizing hormone (LH) is essential for ovulation, acting through extracellular regulated kinase 1/2 (ERK1/2) signaling.
- The specific downstream effectors of ERK1/2 that regulate gene expression during ovulation remain largely uncharacterized.
Purpose of the Study:
- To identify novel LH target genes regulated by the ERK1/2 cascade in ovulatory follicles.
- To elucidate the role of identified genes and histone modifications in LH-induced ovulation.
Main Methods:
- Comparative gene expression profiling of LH-stimulated wild-type versus ERK1/2-deleted ovarian granulosa cells (GCs).
- Analysis of CITED4 protein complex formation and promoter binding.
- Assessment of histone acetylation and deacetylation dynamics (H2B, H3) and their impact on gene expression.
Main Results:
- Cited4 was identified as a novel LH and ERK1/2 target gene, upregulated in an ERK1/2-dependent manner during ovulation.
- CITED4, in complex with CBP, binds to target gene promoters, driving histone acetylation and essential gene expression.
- Histone deacetylases (HDACs) were found to counteract CITED4-CBP activity, regulating gene expression termination.
Conclusions:
- CITED4 is a critical downstream effector of LH/ERK1/2 signaling, indispensable for ovulation.
- LH orchestrates rapid and significant gene expression changes in pre-ovulatory follicles by modulating histone acetylation status via the CITED4-CBP pathway.
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