Arrêt de service lundi 11 juillet de 12h30 à 13h : tous les sites du CCSD (HAL, EpiSciences, SciencesConf, AureHAL) seront inaccessibles (branchement réseau à modifier)
Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

Role of the BAHD1 Chromatin-Repressive Complex in Placental Development and Regulation of Steroid Metabolism

Abstract : BAHD1 is a vertebrate protein that promotes heterochromatin formation and gene repression in association with several epigenetic regulators. However, its physiological roles remain unknown. Here, we demonstrate that ablation of the Bahd1 gene results in hypocholesterolemia, hypoglycemia and decreased body fat in mice. It also causes placental growth restriction with a drop of trophoblast glycogen cells, a reduction of fetal weight and a high neonatal mortality rate. By intersecting transcriptome data from murine Bahd1 knockout (KO) placentas at stages E16.5 and E18.5 of gestation, Bahd1-KO embryonic fibroblasts, and human cells stably expressing BAHD1, we also show that changes in BAHD1 levels alter expression of steroid/lipid metabolism genes. Biochemical analysis of the BAHD1-associated multiprotein complex identifies MIER proteins as novel partners of BAHD1 and suggests that BAHD1-MIER interaction forms a hub for histone deacetylases and methyltransferases, chromatin readers and transcription factors. We further show that overexpression of BAHD1 leads to an increase of MIER1 enrichment on the inactive X chromosome (Xi). In addition, BAHD1 and MIER1/3 repress expression of the steroid hormone receptor genes ESR1 and PGR, both playing important roles in placental development and energy metabolism. Moreover, modulation of BAHD1 expression in HEK293 cells triggers epigenetic changes at the ESR1 locus. Together, these results identify BAHD1 as a core component of a chromatin-repressive complex regulating placental morphogenesis and body fat storage and suggest that its dysfunction may contribute to several human diseases.
Liste complète des métadonnées

Littérature citée [68 références]  Voir  Masquer  Télécharger
Contributeur : Alice Lebreton Connectez-vous pour contacter le contributeur
Soumis le : mardi 2 août 2016 - 11:59:34
Dernière modification le : mardi 14 juin 2022 - 10:37:38
Archivage à long terme le : : mardi 8 novembre 2016 - 19:48:05


Fichiers éditeurs autorisés sur une archive ouverte



Goran Lakisic, Alice Lebreton, Renaud Pourpre, Olivia Wendling, Emanuele Libertini, et al.. Role of the BAHD1 Chromatin-Repressive Complex in Placental Development and Regulation of Steroid Metabolism. PLoS Genetics, Public Library of Science, 2016, 12 (3), pp.e1005898. ⟨10.1371/journal.pgen.1005898⟩. ⟨hal-01350966⟩



Consultations de la notice


Téléchargements de fichiers