Epigenomic Modifications Predict Active Promoters and Gene Structure in Toxoplasma gondii

A new research article appeared today in the open access journal PLoS Pathogens with new insights into the epigenetics modifications regulating gene expression in the human pathogen Toxoplasma gondii:

Apicomplexan parasites, including Toxoplasma gondii, are responsible for a variety of deadly infections, but little is understood about how these important pathogens regulate gene expression. Initial studies suggest that alterations in chromatin structure regulate expression of virulence traits. To understand the relationship of chromatin remodeling and transcriptional regulation in T. gondii, we characterized the histone modifications and gene expression of a contiguous 1% of the T. gondii genome using custom DNA oligonucleotide microarrays. We found that active promoters have a characteristic pattern of histone modifications that correlates strongly with active gene expression in tachyzoites. These data, integrated with prior gene predictions, enable more accurate annotation of the genome and discovery of new genes. Further, these studies illustrate the power of an integrated epigenomic approach to illuminate the role of the “histone code” in regulation of gene expression in the Apicomplexa.

Link

Epigenetics Researcher C. David Allis Grabs Gairdner Award

C. David Allis of The Rockefeller University is one of five scientists to receive a 2007 Gairdner International Award. Allis is recognized for his work on how histones affect genome stability and gene transcription. Each award winner receives US$30,000 and a statue at an award dinner to be held on October 25 in Toronto, Canada.

The “Gairdners,” founded by the late Toronto businessman, James Gairdner, are now in their 48th year. They have grown to be one of the most prestigious international awards for medical research, recognizing outstanding contributions by medical scientists worldwide whose work will significantly improve the quality of life. Of the 283 Gairdner awardees, 68 have gone on to win the Nobel Prize.

C. David Allis is also the editor of the epigenetics textbook released last year by Cold Spring Harbor Press. Link

Histone Modifications Regulate Pluripotency in the Early Mouse Embryo

Earlier this year, a group affiliated with Cambridge University at the Wellcome Trust/Cancer Research UK Gordon Institute reported in Nature that epigenetics, specifically methylation of certain arginine residues of histone H3, directly contribute to cell fate and success in the four-cell stage embryo in the mouse model. These findings confront the widely accepted paradigm that mammalian embryos begin development with similar, if not identical, cell types which differ only when inside and outside cells form. Furthermore, the findings solidify that epigenetic modifications influence cell direction and determination.

By investigating the belief that epigenetic mechanisms are utilized to support pluripotency, the researchers provided evidence that arginine methylation of histone H3 is at its highest in four-cell blastomeres which contribute to the inner cell mass (ICM), polar trophectoderm and fully develop when joined with chimaeras. Inversely, arginine methylation of histone H3 is lowest in cell progeny which contribute primarily to mural trophectoderm which exhibit abnormal development when joined with chimaeras. This finding indicates that maximal levels of arginine methylation of histone H3 influence blastomeres’ contribution to pluripotent cells of the inner cell mass. Furthermore, over-expression of the histone H3 arginine methyltransferase gene CARM1 in blastomeres resulted in direction of subsequent progeny cells to the ICM – solidifying the theory that “specific histone modifications are the earliest known epigenetic marker contributing to development of ICM” and precede formation of inside and outside cells.

References:

Torres-Padilla ME, Parfitt DE, Kouzarides T, Zernicka-Goetz M. 2007. Histone arginine methylation regulates pluripotency in the early mouse embryo. Nature 445:214-218.
doi:10.1038/nature05458