title: EcR recruits dMi-2 and increases efficiency of dMi-2-mediated remodelling to constrain transcription of hormone-regulated genes.
abstract: Gene regulation by steroid hormones plays important roles in health and disease. In Drosophila, the hormone ecdysone governs transitions between key developmental stages. Ecdysone-regulated genes are bound by a heterodimer of ecdysone receptor (EcR) and Ultraspiracle. According to the bimodal switch model, steroid hormone receptors recruit corepressors in the absence of hormone and coactivators in its presence. Here we show that the nucleosome remodeller dMi-2 is recruited to ecdysone-regulated genes to limit transcription. Contrary to the prevalent model, recruitment of the dMi-2 corepressor increases upon hormone addition to constrain gene activation through chromatin remodelling. Furthermore, EcR and dMi-2 form a complex that is devoid of Ultraspiracle. Unexpectedly, EcR contacts the dMi-2 ATPase domain and increases the efficiency of dMi-2-mediated nucleosome remodelling. This study identifies a non-canonical EcR-corepressor complex with the potential for a direct regulation of ATP-dependent nucleosome remodelling by a nuclear hormone receptor.
authors.affiliation: Institute of Molecular Biology and Tumour Research, Philipps University Marburg, Marburg 35037, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Kreher
authors.affiliation: Institute of Molecular Biology and Tumour Research, Philipps University Marburg, Marburg 35037, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Kovač
authors.affiliation: Institute of Molecular Biology and Tumour Research, Philipps University Marburg, Marburg 35037, Germany.
authors.forename: Karim
authors.initials: K
authors.lastname: Bouazoune
authors.affiliation: Institute of Molecular Biology and Tumour Research, Philipps University Marburg, Marburg 35037, Germany.
authors.forename: Igor
authors.initials: I
authors.lastname: Mačinković
authors.affiliation: Institute of Molecular Biology and Tumour Research, Philipps University Marburg, Marburg 35037, Germany.
authors.forename: Anna Luise
authors.initials: AL
authors.lastname: Ernst
authors.affiliation: Institute of Molecular Biology and Tumour Research, Philipps University Marburg, Marburg 35037, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Engelen
authors.affiliation: Institute of Medical Biometry and Epidemiology, Philipps University Marburg, Marburg 35037, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Pahl
authors.affiliation: Center for Tumour Biology and Immunology, Philipps University Marburg, Marburg 35043, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Finkernagel
authors.affiliation: Institute of Molecular Biology and Tumour Research, Philipps University Marburg, Marburg 35037, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Murawska
authors.affiliation: Institute of Molecular Biology and Tumour Research, Philipps University Marburg, Marburg 35037, Germany.
authors.forename: Ikram
authors.initials: I
authors.lastname: Ullah
authors.affiliation: Institute of Molecular Biology and Tumour Research, Philipps University Marburg, Marburg 35037, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Brehm
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001324:Autoantigens / Q000502:physiology*; D002843:Chromatin / Q000378:metabolism; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins / Q000502:physiology*; D004440:Ecdysone / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D007700:Kinetics; D011987:Receptors, Steroid / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D015533:Transcriptional Activation
chemical_list: D001324:Autoantigens; D002843:Chromatin; D029721:Drosophila Proteins; C116095:Mi-2 protein, Drosophila; D011987:Receptors, Steroid; C055469:ecdysone receptor; D004440:Ecdysone; D000251:Adenosine Triphosphatases