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

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dc.contributor.advisor Kristen M. Johansen
dc.contributor.author Li, Yeran
dc.contributor.department Biochemistry, Biophysics and Molecular Biology
dc.date 2018-08-11T16:58:32.000
dc.date.accessioned 2020-06-30T02:56:14Z
dc.date.available 2020-06-30T02:56:14Z
dc.date.copyright Thu Jan 01 00:00:00 UTC 2015
dc.date.embargo 2001-01-01
dc.date.issued 2015-01-01
dc.description.abstract <p>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.</p> <p>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.</p> <p>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.</p>
dc.format.mimetype application/pdf
dc.identifier archive/lib.dr.iastate.edu/etd/14368/
dc.identifier.articleid 5375
dc.identifier.contextkey 7907244
dc.identifier.doi https://doi.org/10.31274/etd-180810-3920
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath etd/14368
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/28553
dc.language.iso en
dc.source.bitstream archive/lib.dr.iastate.edu/etd/14368/Li_iastate_0097E_14806.pdf|||Fri Jan 14 20:19:02 UTC 2022
dc.subject.disciplines Cell Biology
dc.subject.keywords Molecular, Cellular and Developmental Biology
dc.subject.keywords Chromatin remodeling
dc.subject.keywords H3S10 phosphorylation
dc.subject.keywords Histone
dc.title Regulation of gene expression and chromatin structure by JIL-1 mediated histone H3 serine10 phosphorylation in Drosophila
dc.type article
dc.type.genre dissertation
dspace.entity.type Publication
relation.isOrgUnitOfPublication faf0a6cb-16ca-421c-8f48-9fbbd7bc3747
thesis.degree.discipline Molecular, Cellular and Developmental Biology
thesis.degree.level dissertation
thesis.degree.name Doctor of Philosophy
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