title: The imitation switch ATPase Snf2l is required for superovulation and regulates Fgl2 in differentiating mouse granulosa cells.
abstract: Imitation switch (ISWI) proteins are catalytic subunits of chromatin remodeling complexes that alter nucleosome positioning by hydrolyzing ATP to regulate access to DNA. In mice, there are two paralogs, SNF2-homolog (SNF2H) and SNF2-like (SNF2L), which participate in different complexes and have contrasting patterns of expression. Here we investigate the role of SNF2L in ovaries by characterizing a mouse bearing an inactivating deletion of exon 6 that disrupts the ATPase domain. Snf2l mutant mice produce significantly fewer eggs than control mice when superovulated. Gonadotropin stimulation leads to a significant deficit in secondary follicles and an increase in abnormal antral follicles. Mutant females also failed to induce fibrinogen-like 2 (Fgl2) in response to human chorionic gonadotropin (hCG) stimulation, while overexpression of SNF2L was sufficient to drive its expression in granulosa cells. SNF2L was also shown to directly interact with the nuclear receptor co-activator flightless I (FLI-I) as shown by immunoprecipitation. These results begin to establish a role for SNF2L in the precise coordination of gene expression in granulosa cells during folliculogenesis and its broader implications in fertility.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Pépin
authors.forename: François
authors.initials: F
authors.lastname: Paradis
authors.forename: Carol
authors.initials: C
authors.lastname: Perez-Iratxeta
authors.forename: David J
authors.initials: DJ
authors.lastname: Picketts
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Vanderhyden
mesh_terms: D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005091:Exons; D005260:Female; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism*; D006107:Granulosa Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics / Q000378:metabolism; D013480:Superovulation / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D006063:Chorionic Gonadotropin; D004268:DNA-Binding Proteins; C490637:Fgl2 protein, mouse; C497426:Fli1 protein, mouse; D051789:Proto-Oncogene Protein c-fli-1; C499335:Smarca1 protein, mouse; D014157:Transcription Factors; D005340:Fibrinogen
keywords: FGL2; FLI-I; ISWI; SMARCA1; Snf2l; folliculogenesis; superovulation