Regulation of gene expression and chromatin structure by JIL-1 mediated histone H3 serine10 phosphorylation in Drosophila

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Li, Yeran
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Kristen M. Johansen
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Biochemistry, Biophysics and Molecular Biology

The Department of Biochemistry, Biophysics, and Molecular Biology was founded to give students an understanding of life principles through the understanding of chemical and physical principles. Among these principles are frontiers of biotechnology such as metabolic networking, the structure of hormones and proteins, genomics, and the like.

The Department of Biochemistry and Biophysics was founded in 1959, and was administered by the College of Sciences and Humanities (later, College of Liberal Arts & Sciences). In 1979 it became co-administered by the Department of Agriculture (later, College of Agriculture and Life Sciences). In 1998 its name changed to the Department of Biochemistry, Biophysics, and Molecular Biology.

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  • Department of Biochemistry and Biophysics (1959–1998)

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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.

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