Epigenetic processes, such as histone modifications, play essential roles in regulating chromatin structure and gene expression. In Drosophila JIL-1 tandem kinase has been identified as a major regulator of chromatin structure and gene expression. It has been demonstrated that JIL-1 is responsible for histone H3 serine 10 (H3S10) phosphorylation at interphase, which counteracts gene silencing marker histone H3 lysine 9 (H3K9) dimethylation. In addition, JIL- 1 localizes specifically to euchromatic interband regions, and a reduction in JIL-1 levels lead to a global disruption of chromatin morphology.

JIL-1 can be divided into four domains, including an NH2- terminal domain (NTD), two kinase domains (KDI and KDII), and a COOH-terminal domain (CTD). Functions of all four domains have been characterized. The NTD is essential for JIL-1 kinase activity; a truncated JIL-1 protein without the NTD fails to phosphorylate H3S10 despite its proper localization on the chromosome and the presence of both kinase domains. Both kinase domains are required for JIL-1's kinase activity and have equal importance. The CTD is sufficient for JIL's localization to chromosome, but not required for kinase activity.

Furthermore, to explore the mechanisms of JIL-1 mediated histone modification and its interplay with other histone markers, we have conducted a genome-wide study of relationships between JIL-1 mediated H3S10 phosphorylation and H3K9 dimethylation in binding profiles and gene expression. Utilizing ChIP-seq, we show that the H3S10 phosphorylation marker is localized predominantly to active genes, whereas the silencing H3K9 dimethylation marker is enriched at inactive genes. Additionally, studying the transcription profile using RNA-seq reveals functions of JIL-1 in maintaining a balance between active and inactive transcribed genes, where down-regulation of genes in the JIL-1 mutant is associated with elevated levels of H3K9 dimethylation, whereas up-regulation of genes is correlated with loss of H3K9 dimethylation. These results support a model where gene expression levels are regulated by H3K9 dimethylation independent of the state of H3S10 phosphorylation, which in turn functions to indirectly maintain active transcription by counteracting H3K9 dimethylation.