Penn Veterinary Medicine | University of Pennsylvania

Description of Research Expertise

Description of Research Expertise

RESEARCH INTERESTS

Research in my Laboratory is focused on:

I.) Regulation of Large-Scale Chromatin Structure and Epigenetic Control of Gene Expression during Oogenesis

Chromatin configuration in the nucleus or germinal vesicle (GV) of mammalian oocytes undergoes dynamic epigenetic modifications during oocyte growth. A crucial developmental transition at the culmination of oogenesis, large-scale chromatin remodeling in the GV is essential to confer the female gamete with meiotic and developmental potential. Using several models for the experimental manipulation of chromatin structure and function in combination with cell and molecular biology approaches our current work seeks to determine the cellular pathways and factors that are involved in remodeling chromatin in the mammalian oocyte genome.


II). Role of Chromatin Modifications during Meiosis

Centromeric heterochromatin formation is essential for chromosome architecture, transcriptional silencing and chromosome segregation.
However, little is known concerning the epigenetic control of heterochromatin formation in the mammalian germ line. Using RNA interference (RNAi) we have begun to explore the role of ATRX, (a heterochromatin binding protein with chromatin remodeling activity) during meiosis. ATRX is present at centromeric domains in the germinal vesicle of mouse oocytes and becomes exclusively associated with centromeres of chromosomes at metaphase I or metaphase II of meiosis, where it is required to mediate chromosome-microtubule interactions in the female gamete. Moreover, we currently study the role of the lymphocyte-specific helicase (LSH) on meiotic chromosome synapsis, heterochromatin formation and maintenance of genomic stability in the female germ line.

KEY WORDS:
Meiosis, chromatin remodeling, centromeric heterochromatin, epigenetic modifications

Laboratory Members:

Claudia Baumann Ph.D. (Charite, Universitätsmedizin, Berlin)
Feikun Yang Ph.D. (Ludwig-Maximilians University, Munich


Selected Publications:

Baumann C and De La Fuente R* (2008) ATRX marks the inactive X chromosome (Xi) in somatic cells and during imprinted X chromosome inactivation in trophoblast stem cells. Chromosoma (In Press). *Corresponding Author

Baumann C, Schmidtmann A, Muegge K and De La Fuente R* (2008) Association of ATRX with pericentric heterochromatin and the Y Chromosome of Neonatal Mouse Spermatogonia BMC Mol Biol 2008, 9:29 (1-18) *Corresponding Author

*De La Fuente R, Baumann C, Fan T, Schmidtmann A, Dobrinski I, Muegge K (2006) Lsh is required for meiotic chromosome synapsis and retrotransposon silencing in female germ cells. Nature Cell Biology (8);12:1448-1454. *Corresponding Author

De La Fuente R. 2006. Chromatin modifications in the germinal vesicle
(GV) of mammalian oocytes. Dev Biol 292:1-12.

Yang F., De La Fuente R., Leu NA., Baumann C., McLaughlin KJ., Wang PJ. (2006) SYCP2 is required for synaptonemal complex assembly and chromosomal synapsis during male meiosis. J Cell Biol 173 (4):497-507.

*De La Fuente R, Viveiros, MM, Wigglesworth, K and Eppig, JJ (2004) ATRX, a Member of the SNF2 Family of Helicase /ATPases, is required for Chromosome Alignment and Meiotic Spindle Organization in Metaphase II Stage Mouse Oocytes. Dev Biol 272: 1-14. *Corresponding Author

*De La Fuente R, Viveiros MM, Burns KH, Adashi EY, Matzuk MM, and Eppig JJ (2004) Major Chromatin Remodeling in the Germinal Vesicle (GV) of Mammalian Oocytes is Dispensable for Global Transcriptional Silencing but Required for Centromeric Heterochromatin Function. Dev Biol 275:447-458. *Corresponding Author

Tanaka M, Kihara M, Hennebold JD, Eppig JJ, Viveiros MM, Emery BR, Carrell DT, Kirkman NJ, Zhou J, Bondy CA, Becker M, Misteli T, Schultz RM, De La Fuente R, King GJ and Adashi EY. 2005. Expression of the oocyte-specific H1 linker histone gene (mH1fo) is temporally coupled to the initiation of oocyte growth. Biol Reprod 72(1):135-42.

Hübner K, Fuhrmann G., Christenson LK, Kehler J, Reinbold R, De La Fuente R, Wood J, Strauss, III J, Boiani M, and Schöler HR. 2003. Mouse Embryonic Stem Cells in Culture give rise to Oocytes. Science, 300:
1251-1256.

Libby BJ, Cobb J, De La Fuente R, O'Brien M, Wigglesworth K, Handel MA, Eppig JJ, Schimenti JC. 2002. The mouse meiotic mutation mei 1 disrupts chromosome synapsis with sexually dimorphic consequences for meiotic progression. Dev Biol 242(2):174-87.

De La Fuente R, Eppig JJ. 2001. Transcriptional activity of the mouse oocyte genome: companion granulosa cells modulate transcription and chromatin remodeling. Dev Biol 229:224-236.

De La Fuente R, O'Brien MJ, Eppig JJ. 1999. Epidermal growth factor enhances preimplantation developmental competence of maturing mouse oocytes. Hum Reprod 14(12):3060-3068.

De La Fuente R, Hahnel A, Basrur PK, King WA. 1999. X inactive-specific transcript (Xist) expression and X chromosome inactivation in the pre-attachment bovine embryo. Biol Reprod 60:769-775.

De La Fuente R, King WA. 1998. Developmental consequences of karyokinesis without cytokinesis during the first mitotic cell cycle in bovine parthenotes. Biol Reprod 58:952-962.

Winger Q, De La Fuente R, King WA, Armstrong DT, Watson AJ. 1997.
Bovine parthenogenesis is characterized by abnormal chromosomal
complements: Implications for maternal and paternal co-dependence during early bovine development. Dev Genet 21:160-166.

De La Fuente R, King WA. 1997. Use of a chemically defined system for the direct comparison of ICM and trophectoderm distribution in murine, porcine and bovine embryos. Zygote 5:309-320.

Cassar G, De La Fuente R, Yu Z, King GJ, King WA. 1995. Sex chromosome complement and developmental diversity in pre- and post-hatching porcine embryos. Theriogenology 44:879-884.


Book Chapters
Eppig JJ, Viveiros MM, Marin-Bivens C and De La Fuente R. 2003.
Regulation of Mammalian Oocyte Maturation. In: The Ovary. P. Long and E.Y. Adashi. Eds. Elsevier, Science. San Diego California.

Selected Publications

Baumann C., Schmidtmann A., Muegge K. and De La Fuente R*: Association of ATRX with pericentric heterochromatin and the Y Chromosome of Neonatal Mouse Spermatogonia *Corresponding Author BMC Mol Biol 9(29): 1-19, 2008.

Baumann C. and De La Fuente R*: ATRX marks the inactive X chromosome (Xi) in somatic cells and during imprinted X chromosome inactivation in trophoblast stem cells *Corresponding Author Chromosoma (In Press) 2008.

De La Fuente R.: Chromatin modifications in the germinal vesicle (GV) of mammalian oocytes. Dev Biol. 292: 1-12, 2006.

Baumann, C and De La Fuente, R.: Independent regulation of DNA methylation and histone methylation in the chromosomes of murine neonatal spermatogonia. Biology of Reproduction 2006.

Yang F., De La Fuente R., Leu NA., Baumann C., McLaughlin KJ., Wang PJ.: SYCP2 is required for synaptonemal complex assembly and chromosomal synapsis during male meiosis. J Cell Biol 173(4): 497-507, 2006.

*De La Fuente R., Baumann C., Fan T., Schmidtmann A., Dobrinski I., Muegge K.: Lsh is required for meiotic chromosome synapsis and retrotransposon silencing in female germ cells. Nature Cell Biology 8(12): 1448-1454, 2006.

Baumann, C and De La Fuente, R.: Ontogeny of the chromatin remodeling protein (ATRX) and its potential interaction with death-domain associated protein (DAXX) during mouse spermatogenesis. Biology of Reproduction 2005.

Tanaka M, Kihara M, Hennebold JD, Eppig JJ, Viveiros MM, Emery BR, Carrell DT, Kirkman NJ, Zhou J, Bondy CA, Becker M, Misteli T, Schultz RM, De La Fuente R, King GJ and Adashi EY.: Expression of the oocyte-specific H1 linker histone gene (mH1fo) is temporally coupled to the initiation of oocyte growth. Biol Reprod 72(1): 135-142, 2005.

*De La Fuente R, Viveiros MM, Wigglesworth K and Eppig JJ.: ATRX, a Member of the SNF2 Family of Helicase /ATPases, is required for Chromosome Alignment and Meiotic Spindle Organization in Metaphase II Stage Mouse Oocytes. Dev Biol 272: 1-14, 2004.

*De La Fuente R, Viveiros MM, Burns KH, Adashi EY, Matzuk MM, and Eppig JJ.: Major Chromatin Remodeling in the Germinal Vesicle (GV) of Mammalian Oocytes is Dispensable for Global Transcriptional Silencing but Required for Centromeric Heterochromatin Function. Dev Biol 275: 447-458, 2004.