Regulation of Gdnf expression by retinoic acid in Sertoli cells.
Rossana SaracinoChiara CapponiSara Di PersioCarla BoitaniSilvia MasciarelliFrancesco FaziStefania FeraElena ViciniPublished in: Molecular reproduction and development (2020)
Glial cell line-derived neurotrophic factor (GDNF) and retinoic acid (RA) are two molecules crucial for the regulation of the spermatogonial compartment of the testis. During the cycle of the seminiferous epithelium, their relative concentration oscillates with lower GDNF levels in stages where RA levels are high. It has been recently shown that RA negatively regulates Gdnf expression but the mechanisms behind are so far unknown. Here, we show that RA directly downregulates Gdnf mRNA levels in primary murine Sertoli cells through binding of RARα to a novel DR5-RARE on Gdnf promoter. Pharmacological inhibition and chromatin immunoprecipitation-quantitative polymerase chain reaction analysis suggested that the underlying mechanism involved histone deacetylase activity and epigenetic repression of Gdnf promoter upon RA treatment.
Keyphrases
- rheumatoid arthritis
- gene expression
- disease activity
- induced apoptosis
- dna methylation
- poor prognosis
- histone deacetylase
- transcription factor
- ankylosing spondylitis
- binding protein
- cell cycle arrest
- interstitial lung disease
- oxidative stress
- systemic lupus erythematosus
- dna damage
- genome wide
- high resolution
- systemic sclerosis
- long non coding rna
- spinal cord injury
- mass spectrometry
- cell proliferation
- replacement therapy