Identification of a pituitary ERα-activated enhancer triggering the expression of Nr5a1, the earliest gonadotrope lineage-specific transcription factor - Université Paris Cité Accéder directement au contenu
Article Dans Une Revue Epigenetics & Chromatin Année : 2019

Identification of a pituitary ERα-activated enhancer triggering the expression of Nr5a1, the earliest gonadotrope lineage-specific transcription factor

Résumé

Background: Gonadotrope lineage differentiation is a stepwise process taking place during pituitary development. The early step of gonadotrope lineage specification is characterized by the expression of the Nr5a1 transcription factor , a crucial factor for gonadotrope cell fate determination. Abnormalities affecting Nr5a1 expression lead to hypo-gonadotropic hypogonadism and infertility. Although significant knowledge has been gained on the signaling and transcriptional events controlling gonadotrope differentiation, epigenetic mechanisms regulating Nr5a1 expression during early gonadotrope lineage specification are still poorly understood. Results: Using ATAC chromatin accessibility analyses on three cell lines recapitulating gradual stages of gonadotrope differentiation and in vivo on developing pituitaries, we demonstrate that a yet undescribed enhancer is transiently recruited during gonadotrope specification. Using CRISPR/Cas9, we show that this enhancer is mandatory for the emergence of Nr5a1 during gonadotrope specification. Furthermore, we identify a highly conserved estrogen-binding element and demonstrate that the enhancer activation is dependent upon estrogen acting through ERα. Lastly, we provide evidence that binding of ERα is crucial for chromatin remodeling of Nr5a1 enhancer and promoter, leading to RNA polymerase recruitment and transcription. Conclusion: This study identifies the earliest regulatory sequence involved in gonadotrope lineage specification and highlights the key epigenetic role played by ERα in this differentiation process.
Fichier principal
Vignette du fichier
Papier.pdf (4.65 Mo) Télécharger le fichier
Origine : Publication financée par une institution
Loading...

Dates et versions

hal-02359520 , version 1 (12-11-2019)

Licence

Paternité

Identifiants

Citer

Vincent Pacini, Florence Petit, Bruno Querat, Jean-Noël Laverrière, Joëlle Cohen-Tannoudji, et al.. Identification of a pituitary ERα-activated enhancer triggering the expression of Nr5a1, the earliest gonadotrope lineage-specific transcription factor. Epigenetics & Chromatin, 2019, 12 (1), ⟨10.1186/s13072-019-0291-8⟩. ⟨hal-02359520⟩
35 Consultations
58 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More