Histone lysine methyltransferases and demethylases in Plasmodium falciparum. Export

@article{citeulike:2651121, abstract = {Dynamic histone lysine methylation, regulated by methyltransferases and demethylases, plays fundamental roles in chromatin structure and gene expression in a wide range of eukaryotic organisms. A large number of SET-domain-containing proteins make up the histone lysine methyltransferase (HKMT) family, which catalyses the methylation of different lysine residues with relatively high substrate specificities. Another large family of Jumonji C (JmjC)-domain-containing histone lysine demethylases (JHDMs) reverses histone lysine methylation with both lysine site and methyl-state specificities. Through bioinformatic analysis, at least nine SET-domain-containing genes were found in the malaria parasite Plasmodium falciparum and its sibling species. Phylogenetic analysis separated these putative HKMTs into five subfamilies with different putative substrate specificities. Consistent with the phylogenetic subdivision, methyl marks were found on K4, K9 and K36 of histone H3 and K20 of histone H4 by site-specific methyl-lysine antibodies. In addition, most SET-domain genes and histone methyl-lysine marks displayed dynamic changes during the parasite asexual erythrocytic cycle, suggesting that they constitute an important epigenetic mechanism of gene regulation in malaria parasites. Furthermore, the malaria parasite and other apicomplexan genomes also encode JmjC-domain-containing proteins that may serve as histone lysine demethylases. Whereas prokaryotic expression of putative active domains of four P. falciparum SET proteins did not yield detectable HKMT activity towards recombinant P. falciparum histones, two protein domains expressed in vitro in a eukaryotic system showed HKMT activities towards H3 and H4, respectively. With the discovery of these Plasmodium SET- and JmjC-domain genes in the malaria parasite genomes, future efforts will be directed towards elucidation of their substrate specificities and functions in various cellular processes of the parasites.}, address = {Department of Entomology, The Pennsylvania State University, 501 ASI Building, University Park, PA 16802, USA.}, author = {Cui, Liwang and Fan, Qi and Cui, Long and Miao, Jun}, citeulike-article-id = {2651121}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.ijpara.2008.01.002}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18299133}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18299133}, day = {26}, doi = {10.1016/j.ijpara.2008.01.002}, issn = {0020-7519}, journal = {International journal for parasitology}, keywords = {chromatin, crps, epigenetics, histone, methylation, parasite, protist}, month = {January}, posted-at = {2008-04-10 23:14:48}, priority = {5}, title = {Histone lysine methyltransferases and demethylases in Plasmodium falciparum.}, url = {http://dx.doi.org/10.1016/j.ijpara.2008.01.002}, year = {2008} }

TY - JOUR ID - citeulike:2651121 L3 - citeulike-article-id:2651121 N2 - Dynamic histone lysine methylation, regulated by methyltransferases and demethylases, plays fundamental roles in chromatin structure and gene expression in a wide range of eukaryotic organisms. A large number of SET-domain-containing proteins make up the histone lysine methyltransferase (HKMT) family, which catalyses the methylation of different lysine residues with relatively high substrate specificities. Another large family of Jumonji C (JmjC)-domain-containing histone lysine demethylases (JHDMs) reverses histone lysine methylation with both lysine site and methyl-state specificities. Through bioinformatic analysis, at least nine SET-domain-containing genes were found in the malaria parasite Plasmodium falciparum and its sibling species. Phylogenetic analysis separated these putative HKMTs into five subfamilies with different putative substrate specificities. Consistent with the phylogenetic subdivision, methyl marks were found on K4, K9 and K36 of histone H3 and K20 of histone H4 by site-specific methyl-lysine antibodies. In addition, most SET-domain genes and histone methyl-lysine marks displayed dynamic changes during the parasite asexual erythrocytic cycle, suggesting that they constitute an important epigenetic mechanism of gene regulation in malaria parasites. Furthermore, the malaria parasite and other apicomplexan genomes also encode JmjC-domain-containing proteins that may serve as histone lysine demethylases. Whereas prokaryotic expression of putative active domains of four P. falciparum SET proteins did not yield detectable HKMT activity towards recombinant P. falciparum histones, two protein domains expressed in vitro in a eukaryotic system showed HKMT activities towards H3 and H4, respectively. With the discovery of these Plasmodium SET- and JmjC-domain genes in the malaria parasite genomes, future efforts will be directed towards elucidation of their substrate specificities and functions in various cellular processes of the parasites. JF - International journal for parasitology SN - 0020-7519 AD - Department of Entomology, The Pennsylvania State University, 501 ASI Building, University Park, PA 16802, USA. TI - Histone lysine methyltransferases and demethylases in Plasmodium falciparum. KW - chromatin KW - crps KW - epigenetics KW - histone KW - methylation KW - parasite KW - protist AU - Cui, Liwang AU - Fan, Qi AU - Cui, Long AU - Miao, Jun PY - 2008/01/26/ UR - http://dx.doi.org/10.1016/j.ijpara.2008.01.002 ER -