PARENT SESSION
SLIDE SESSION 17: PREIMPLANTATION DEVELOPMENT
Chairs: Richard Leach, Carol Brenner, David Natale (Trainee)
Arts Hall 026
1:30 PM-3:30 PM

ACETYLATION AND METHYLATION UPREGULATES THE EXPRESSION OF IMPRINTED GENES DURING MOUSE PREIMPLANTATION DEVELOPMENT.

Baqir, Senan¹, Smith, Lawrence¹, ¹

ABSTRACT- Genomic imprinting is an epigenetic phenomenon whereby a certain number of genes are expressed either from the paternal or maternal allele. Temporal alterations in DNA methylation during embryogenesis is characterized by a wave of global demethylation from the time of fertilization till implantation followed by another wave of de novo methylation at gastrulation during which the mono allelic pattern of imprinted genes is restored. On the other hand, histone acetylation is often associated with increased transcriptional activity of the chromatin and the correlation between methylation and acetylation is not well understood. Therefore, our objective is to characterize the expression pattern of imprinted genes during early development and to determine whether acetylation/methylation influence imprinting expression patterns. For such, we have examined the expression profile of imprinted genes (Igf2r, P57^KIP2 & Peg1), non imprinted genes (Oct4 & Gas6) and a housekeeping gene (Gapdh) in mouse 8-cell embryos supplemented with either TSA (histone deacetylase inhibitor) or 5 Aza-C (DNA demethylation agent). RNA samples were extracted from a pool of 12 embryos, reversed transcribed and the equivalent expression of a single embryo was measured by PCR using a real-time apparatus. Our results demonstrate that the expression of maternally and paternally genes was up-regulated following TSA treatment (5, 7 and 11 fold, for Igf2r, P57^KIP2 and Peg1, respectively) and 5 Aza-C treatment (3, 4 and 10 fold, for Igf2r, P57^KIP2 and Peg1, respectively) whereas the expression of Gapdh remained stable. Moreover, expression of Gas6 increased 10 fold and Oct4 was down regulated (0.5 fold). Together, these results indicate that the expression pattern of imprinted genes can be modified by inhibiting histone deacetylases and by demethylation with 5 Aza-C, suggesting that these two epigenetic markers either overlap or complement each other to regulate the expression of imprinted genes (Funded by NSERC of Canada).

KEY WORDS: Imprinting, Acetylation, Methylation