[
European Worm Meeting,
2008]
A strict regulation of gene expression is essential for cellular identity. and differentiation during development of eukaryotic organisms. At the. level of DNA, gene expression can be regulated by changes in the structure. of chromatin through, for example, post-translational modifications of. histone tails. Among the vast variety of known histone tail modifications,. histone methylation has been shown to be involved in important cellular. processes such as heterochromatin formation, X-chromosome inactivation,. transcriptional regulation and DNA repair. Moreover, aberrant histone. methylation has been linked to several diseases such as cancer.. We are particularly interested in the methylation of histone lysines and. more specifically in the methylation state of lysine 27 at histone 3. (H3K27). The H3K27me3 (tri-methyl) mark, associated to transcriptional. repression, is a unique mark for stem cell state and decreases during. differentiation into somatic cells. While the Polycomb group proteins are. known to mediate tri-methylation of H3K27, the Jumonji C (JmjC) domain-. containing proteins, UTX and JMJD3, were recently shown to catalyze its. demethylation. However, little is known about the biological functions of. these enzymes in vivo.. In C. elegans, four homologs of the human H3K27 demethylases are identified. (D2021.1/utx-1, F18E9.5, C29F7.6, F23D12.5). To determine their in vivo. role(s), mutants and RNA interfered animals of all these homologs were. analyzed. The resulting phenotypes, associated to loss or reduction of. H3K27me3 demethylase activity, point to functional roles during embryonic. and early larval development, in vulva and gonad formation as well as in. fertility. Results from gene expression microarrays, identifying genes. which expression is affected by the loss of histone demethylase activity,. will also be presented at the meeting.
[
Development & Evolution Meeting,
2008]
A strict regulation of gene expression is essential for cellular identity and differentiation during development of eukaryotic organisms. At the level of DNA, gene expression can be regulated by changes in the structure of chromatin through, for example, post-translational modifications of histone tails. Among the vast variety of known histone tail modifications, histone methylation has been shown to be involved in important cellular processes such as heterochromatin formation, X-chromosome inactivation, transcriptional regulation and DNA repair. Moreover, aberrant histone methylation has been linked to several diseases such as cancer. We are particularly interested in the methylation of histone lysines and more specifically in the methylation state of lysine 27 at histone 3 (H3K27). The H3K27me3 (tri-methyl) mark, associated to transcriptional repression, is a unique mark for stem cell state and decreases during differentiation into somatic cells. While the Polycomb group proteins are known to mediate tri-methylation of H3K27, the Jumonji C (JmjC) domain-containing proteins, UTX and JMJD3, were recently shown to catalyze its demethylation. However, little is known about the biological functions of these enzymes in vivo. In C. elegans, four homologs of the human H3K27 demethylases are identified (D2021.1/utx-1, F18E9.5, C29F7.6, F23D12.5). To determine their in vivo role(s), mutants and RNA interfered animals of all these homologs were analyzed. The resulting phenotypes, associated to loss or reduction of H3K27me3 demethylase activity, point to functional roles during embryonic and early larval development, in vulva and gonad formation as well as in fertility. Results from gene expression microarrays, identifying genes which expression is affected by the loss of histone demethylase activity, will also be presented at the meeting.