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Vertebrate reproductive science and technology
RESEARCH ARTICLE (Open Access)

Nuclear trafficking dynamics of Bromodomain-containing protein 7 (BRD7), a switch/sucrose non-fermentable (SWI/SNF) chromatin remodelling complex subunit, in porcine oocytes and cleavage-stage embryos

Jennifer S. Crodian A * , Bethany M. Weldon A * , Yu-Chun Tseng A , Birgit Cabot A and Ryan Cabot https://orcid.org/0000-0002-4790-9655 A B
+ Author Affiliations
- Author Affiliations

A Department of Animal Sciences, Purdue University, 270 South Russell Street, West Lafayette, IN, 47907, USA.

B Corresponding author. Email: rcabot@purdue.edu

Reproduction, Fertility and Development 31(9) 1497-1506 https://doi.org/10.1071/RD19030
Submitted: 22 January 2019  Accepted: 30 March 2019   Published: 13 May 2019

Journal Compilation © CSIRO 2019 Open Access CC BY-NC-ND

Abstract

In the work presented here, we investigated how bromodomain-containing protein 7 (BRD7), a subunit associated with switch/sucrose non-fermentable (SWI/SNF) chromatin remodelling complexes, is trafficked between cellular compartments during embryo development. SWI/SNF complexes are multi-subunit complexes that contain a core catalytic subunit (SWI/SNF related, Matrix associated, Actin dependent Regulator of Chromatin, subfamily A, member 4, or member 2; SMARCA4 or SMARCA2) and a collection of additional subunits that guide the complexes to their appropriate loci; BRD7 is one of these additional subunits. We hypothesised that BRD7 is exported from the nuclei of porcine oocytes and embryos in a Chromosome Region Maintenance 1 (CRM1)-dependent manner and imported into the nuclei using the karyopherin α/β1 heterodimer. Porcine oocytes and embryos were treated with inhibitors of CRM1-mediated nuclear export and karyopherin α/β1-mediated nuclear import to test this hypothesis. An RNA interference assay and a dominant negative overexpression assay were also performed to determine if karyopherin α7 serves a specific role in BRD7 trafficking. Our findings indicate that BRD7 shuttles between nuclear and cytoplasmic compartments during cleavage development. The shuttling of BRD7 indicates that it serves a unique role in remodelling chromatin during this developmental window.

Additional keywords: epigenetic, importin, karyopherin, trafficking, SWI/SNF.


References

Abeydeera, L. R., and Day, B. N. (1997). In vitro penetration of pig oocytes in a modified Tris-buffered medium: effect of BSA, caffeine and calcium. Theriogenology 48, 537–544.
In vitro penetration of pig oocytes in a modified Tris-buffered medium: effect of BSA, caffeine and calcium.Crossref | GoogleScholarGoogle Scholar | 16728149PubMed |

Abeydeera, L. R., Wang, W. H., Prather, R. S., and Day, B. N. (1998). Maturation in vitro of pig oocytes in protein-free culture media: fertilization and subsequent embryo development in vitro. Biol. Reprod. 58, 1316–1320.
Maturation in vitro of pig oocytes in protein-free culture media: fertilization and subsequent embryo development in vitro.Crossref | GoogleScholarGoogle Scholar | 9603270PubMed |

Anderson, J. E., Matteri, R. L., Abeydeera, L. R., Day, B. N., and Prather, R. S. (1999). Cyclin B1 transcript quantitation over the maternal to zygotic transition in both in vivo and in vitro-derived 4-cell stage porcine embryos. Biol. Reprod. 61, 1460–1467.
Cyclin B1 transcript quantitation over the maternal to zygotic transition in both in vivo and in vitro-derived 4-cell stage porcine embryos.Crossref | GoogleScholarGoogle Scholar | 10569990PubMed |

Bartholomew, B. (2014). Regulating the chromatin landscape: structural and mechanistic perspectives. Annu. Rev. Biochem. 83, 671–696.
Regulating the chromatin landscape: structural and mechanistic perspectives.Crossref | GoogleScholarGoogle Scholar | 24606138PubMed |

Bonifaci, N., Moroianu, J., Radu, A., and Blobel, G. (1997). Karyopherin 2 mediates nuclear import of a mRNA binding protein. Proc. Natl. Acad. Sci. USA 94, 5055–5060.
Karyopherin 2 mediates nuclear import of a mRNA binding protein.Crossref | GoogleScholarGoogle Scholar | 9144189PubMed |

Bultman, S., Gebuhr, T. C., Yee, D., Mantia, C. L., Nicholson, J., Gilliam, A., Randazzo, F., Metzger, D., Chambon, P., Crabtree, G., and Magnuson, T. (2000). A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes. Mol. Cell 6, 1287–1295.
A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes.Crossref | GoogleScholarGoogle Scholar | 11163203PubMed |

Bultman, S. J., Gebuhr, T. C., Pan, H., Svoboda, P., Schultz, R. M., and Magnuson, T. (2006). Maternal BRG1 regulates zygotic genome activation in the mouse. Genes Dev. 20, 1744–1754.
Maternal BRG1 regulates zygotic genome activation in the mouse.Crossref | GoogleScholarGoogle Scholar | 16818606PubMed |

Cabot, R. A., and Prather, R. S. (2003). Cleavage stage porcine embryos may have differing developmental requirements for karyopherins α2 and α3. Mol. Reprod. Dev. 64, 292–301.
Cleavage stage porcine embryos may have differing developmental requirements for karyopherins α2 and α3.Crossref | GoogleScholarGoogle Scholar | 12548662PubMed |

Cabot, R. A., Hannink, M., and Prather, R. S. (2002). CRM1-mediated nuclear export is present during porcine embryogenesis, but is not required for early cleavage. Biol. Reprod. 67, 814–819.
CRM1-mediated nuclear export is present during porcine embryogenesis, but is not required for early cleavage.Crossref | GoogleScholarGoogle Scholar | 12193389PubMed |

Cabot, B., Tseng, Y.-C., Crodian, J. S., and Cabot, R. (2017). Differential expression of key subunits of SWI/SNF chromatin remodeling complexes in porcine embryos derived in vitro or in vivo. Mol. Reprod. Dev. 84, 1238–1249.
Differential expression of key subunits of SWI/SNF chromatin remodeling complexes in porcine embryos derived in vitro or in vivo.Crossref | GoogleScholarGoogle Scholar | 29024220PubMed |

Clapier, C. R., and Cairns, B. R. (2009). The biology of chromatin remodeling complexes. Annu. Rev. Biochem. 78, 273–304.
The biology of chromatin remodeling complexes.Crossref | GoogleScholarGoogle Scholar | 19355820PubMed |

Dingwall, C., and Laskey, R. E. (1991). Nuclear targeting sequences-a consensus? Trends Biochem. Sci. 16, 478–481.
Nuclear targeting sequences-a consensus?Crossref | GoogleScholarGoogle Scholar | 1664152PubMed |

Euskirchen, G., Auerbach, R. K., and Snyder, M. (2012). SWI/SNF chromatin-remodeling factors: multiscale analyses and diverse functions. J. Biol. Chem. 287, 30897–30905.
SWI/SNF chromatin-remodeling factors: multiscale analyses and diverse functions.Crossref | GoogleScholarGoogle Scholar | 22952240PubMed |

Fukuda, M., Asano, S., Nakamura, T., Adachi, M., and Nature, Y.-M. (1997). CRM1 is responsible for intracellular transport mediated by the nuclear export signal. Nature 390, 308–311.
CRM1 is responsible for intracellular transport mediated by the nuclear export signal.Crossref | GoogleScholarGoogle Scholar | 9384386PubMed |

Görlich, D., Henklein, P., Laskey, R. A., and Hartmann, E. (1996). A 41 amino acid motif in importin-alpha confers binding to importin-beta and hence transit into the nucleus. EMBO J. 15, 1810–1817.
A 41 amino acid motif in importin-alpha confers binding to importin-beta and hence transit into the nucleus.Crossref | GoogleScholarGoogle Scholar | 8617226PubMed |

Kaeser, M. D., Aslanian, A., Dong, M.-Q., Yates, J., and Emerson, B. M. (2008). BRD7, a novel PBAF-specific SWI/SNF subunit, is required for target gene activation and repression in embryonic stem cells. J. Biol. Chem. 283, 32254–32263.
BRD7, a novel PBAF-specific SWI/SNF subunit, is required for target gene activation and repression in embryonic stem cells.Crossref | GoogleScholarGoogle Scholar | 18809673PubMed |

Kim, Y., Andrés Salazar Hernández, M., Herrema, H., Delibasi, T., and Park, S. W. (2016). The role of BRD7 in embryo development and glucose metabolism. J. Cell. Mol. Med. 20, 1561–1570.
The role of BRD7 in embryo development and glucose metabolism.Crossref | GoogleScholarGoogle Scholar | 27444544PubMed |

Li, E., Bestor, T., and Jaenisch, R. (1992). Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69, 915–926.
Targeted mutation of the DNA methyltransferase gene results in embryonic lethality.Crossref | GoogleScholarGoogle Scholar | 1606615PubMed |

Lott, K., and Cingolani, G. (2011). The importin β binding domain as a master regulator of nucleocytoplasmic transport. Biochim. Biophys. Acta 1813, 1578–1592.
The importin β binding domain as a master regulator of nucleocytoplasmic transport.Crossref | GoogleScholarGoogle Scholar | 21029753PubMed |

Nagl, N. G., Patsialou, A., Haines, D. S., Dallas, P. B., Beck, G. R., and Moran, E. (2005). The p270 (ARID1A/SMARCF1) subunit of mammalian SWI/SNF-related complexes is essential for normal cell cycle arrest. Cancer Res. 65, 9236–9244.
The p270 (ARID1A/SMARCF1) subunit of mammalian SWI/SNF-related complexes is essential for normal cell cycle arrest.Crossref | GoogleScholarGoogle Scholar | 16230384PubMed |

Phelan, M. L., Sif, S., Narlikar, G. J., and Kingston, R. E. (1999). Reconstitution of a core chromatin remodeling complex from SWI/SNF subunits. Mol. Cell 3, 247–253.
Reconstitution of a core chromatin remodeling complex from SWI/SNF subunits.Crossref | GoogleScholarGoogle Scholar | 10078207PubMed |

Prather, R. S., and Schatten, G. (1992). Construction of the nuclear matrix at the transition from maternal to zygotic control of development in the mouse: an immunocytochemical study. Mol. Reprod. Dev. 32, 203–208.
Construction of the nuclear matrix at the transition from maternal to zygotic control of development in the mouse: an immunocytochemical study.Crossref | GoogleScholarGoogle Scholar | 1497870PubMed |

Reyes, J. C., Barra, J., Muchardt, C., Camus, A., Babinet, C., and Yaniv, M. (1998). Altered control of cellular proliferation in the absence of mammalian brahma (SNF2α). EMBO J. 17, 6979–6991.
Altered control of cellular proliferation in the absence of mammalian brahma (SNF2α).Crossref | GoogleScholarGoogle Scholar | 9843504PubMed |

Ribbeck, K., Lipowsky, G., Kent, H. M., Stewar, M., and Gorlich, D. (1998). NTF2 mediates nuclear import of Ran. EMBO J. 17, 6587–6598.
NTF2 mediates nuclear import of Ran.Crossref | GoogleScholarGoogle Scholar | 9822603PubMed |

Sasaki, H., and Matsui, Y. (2008). Epigenetic events in mammalian germ-cell development: reprogramming and beyond. Nat. Rev. Genet. 9, 129–140.
Epigenetic events in mammalian germ-cell development: reprogramming and beyond.Crossref | GoogleScholarGoogle Scholar | 18197165PubMed |

Tejomurtula, J., Lee, K. B., Tripurani, S. K., Smith, G. W., and Yao, J. (2009). Role of importin alpha8, a new member of the importin alpha family of nuclear transport proteins, in early embryonic development in cattle. Biol. Reprod. 81, 333–342.
Role of importin alpha8, a new member of the importin alpha family of nuclear transport proteins, in early embryonic development in cattle.Crossref | GoogleScholarGoogle Scholar | 19420384PubMed |

Wagstaff, K. M., Sivakumaran, H., Heaton, S. M., Harrich, D., and Jans, D. A. (2012). Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochem. J. 443, 851–856.
Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus.Crossref | GoogleScholarGoogle Scholar | 22417684PubMed |

Wang, K., Sengupta, S., Magnani, L., Wilson, C. A., Henry, R. W., and Knott, J. G. (2010). Brg1 is required for Cdx2-mediated repression of Oct4 expression in mouse blastocysts. PLoS One 5, e10622.
Brg1 is required for Cdx2-mediated repression of Oct4 expression in mouse blastocysts.Crossref | GoogleScholarGoogle Scholar | 21209939PubMed |

Wang, X., Park, K. E., Koser, S., Liu, S., Magnani, L., and Cabot, R. A. (2012). KPNA7, an oocyte-and embryo-specific karyopherin subtype, is required for porcine embryo development. Reprod. Fertil. Dev. 24, 382–391.
KPNA7, an oocyte-and embryo-specific karyopherin subtype, is required for porcine embryo development.Crossref | GoogleScholarGoogle Scholar | 22281085PubMed |

Wilsker, D., Probst, L., Wain, H. M., Maltais, L., Tucker, P. W., and Moran, E. (2005). Nomenclature of the ARID family of DNA-binding proteins. Genomics 86, 242–251.
Nomenclature of the ARID family of DNA-binding proteins.Crossref | GoogleScholarGoogle Scholar | 15922553PubMed |

Yoshioka, K., Suzuki, C., Tanaka, A., Anas, I., and Iwamura, S. (2002). Birth of piglets derived from porcine zygotes cultured in a chemically defined medium. Biol. Reprod. 66, 112–119.
Birth of piglets derived from porcine zygotes cultured in a chemically defined medium.Crossref | GoogleScholarGoogle Scholar | 11751272PubMed |

Yuan, Y., Spate, L. D., Redel, B. K., Tian, Y., Zhou, J., Prather, R. S., and Roberts, R. M. (2017). Quadrupling efficiency in production of genetically modified pigs through improved oocyte maturation. Proc. Natl. Acad. Sci. USA 114, E5796–E5804.
Quadrupling efficiency in production of genetically modified pigs through improved oocyte maturation.Crossref | GoogleScholarGoogle Scholar | 28673989PubMed |

Zhou, M., Guo, C., Li, X., He, J., Xu, X., Wang, H., Tang, K., Cao, L., and Li, G. (2011). Definition and function identification of nucleus export signal of BRD7. Zhong Nan Da Xue Xue Bao Yi Xue Ban 36, 634–639.
| 21873788PubMed |