title: CECR2 is involved in spermatogenesis and forms a complex with SNF2H in the testis.
abstract: The regulation of nucleosome positioning and composition by ATP-dependent chromatin remodeling enzymes and their associated binding partners plays important biological roles in mammals. CECR2 is a binding partner to the ISWI (imitation switch) ATPase SNF2L/SMARCA1 and is involved in neural tube closure and inner ear development; however, its functions in adult tissues have not been examined. Here, we report that CECR2 contributes to spermatogenesis and forms a complex that includes the other ISWI ATPase SNF2H/SMARCA5 in the testis. Cecr2 mutant males non-penetrant for neural tube defects sired smaller litters than wild-type males. Strikingly, while we found that Cecr2 mutants have normal seminiferous epithelium morphology, sperm count, motility, and morphology, the mutant spermatozoa were compromised in their ability to fertilize oocytes. Investigation of CECR2/ISWI complexes in the testis showed that SNF2H interacted with CECR2, and this interaction was also observed in embryonic stem cells, suggesting that CECR2 may interact with SNF2H or SNF2L depending on the cell type. Finally, we found that Cecr2 mutants exhibit misregulation of the homeobox transcription factor Dlx5 in the testis, suggesting that CECR2 complexes may regulate gene expression during spermatogenesis. Taken together, our results demonstrate a novel role of CECR2-containing complexes in spermatogenesis and show that CECR2 interacts predominantly with SNF2H instead of SNF2L in the testis.
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2E9.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Thompson
authors.forename: Kacie A
authors.initials: KA
authors.lastname: Norton
authors.forename: Farshad H
authors.initials: FH
authors.lastname: Niri
authors.forename: Christine E
authors.initials: CE
authors.lastname: Dawe
authors.forename: Heather E
authors.initials: HE
authors.lastname: McDermid
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D007248:Infertility, Male / Q000378:metabolism / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D012670:Seminiferous Epithelium / Q000166:cytology / Q000378:metabolism; D013076:Sperm Count; D013081:Sperm Motility; D013091:Spermatogenesis; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C501837:CECR2 protein, mouse; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C501120:Dlx5 protein, mouse; D018398:Homeodomain Proteins; C086468:ISWI protein; D036341:Intercellular Signaling Peptides and Proteins; C499335:Smarca1 protein, mouse; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; C498725:Smarca5 protein, mouse