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Andrea Ebert-McNeill
Sara P Clark
James J Miller
Paige Birdsall
Manisha Chandar
Elizabeth A Cerny
Patricia H Hall
Maribeth H Johnson
Carlos Isales
Norman Chutkan
Maryka H Bhattacharyya
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, 3 February 2012, Pages 793–806
CECR2 Is Involved in Spermatogenesis and Forms a Complex with SNF2H in the Testis, , , , ,
Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2E9The 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 i 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.Highlights? We examined the role of chromatin remodeling protein CECR2 in the germ line. ? Cecr2 mutant males sired smaller-sized litters than wild-type males. ? Loss of CECR2 compromised the ability of mature spermatozoa to fertilize oocytes. ? CECR2 formed a complex with ISWI ATPase SNF2H in the testis and ES cells. ? We conclude that CECR2 contributes to spermatogenesis and interacts with SNF2H.AbbreviationsXgal, 5-bromo-4-chloro-3-indolyl-β,d-galactopyranoside; RT, reverse transcriptase; qRT-PCR, quantitative RT-PCR; IP, immunoprecipitationKeywordsCECR2; SNF2H/SMARCA5 SNF2L/SMARCA1; ISWI; spermatogenesis; chromatin remodeling
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