Date of Award
Doctor of Philosophy
Zoology and Genetics
Molecular, Cellular, and Developmental Biology
Kristen M. Johansen
The Drosophila JIL-1 tandem Ser/Thr kinase is associated with chromosomes/chromatin throughout the cell cycle in early embryos and localized to hundreds of sites on the open interband regions on third instar larvae polytene chromosomes. Interestingly, the level of JIL-1 is upregulated on the male X chromosome, which is hypertranscribed for dosage compensation. The distribution of JIL-1 overlaps with that of MSL (male specific lethal) proteins and JIL-1 is associated with the MSL complex.;To further study the function of JIL-1 in vivo, a series of JIL-1 mutants from hypomorphs to null were generated. Analyzing the phenotypes of JIL-1 mutants, we found that JIL-1 is required for the viability of both females and males. Moreover, in the surviving flies of JIL-1 hypomorphic mutants, the number of males is less than that of females, implicating that JIL-1 plays a role in dosage compensation. JIL-1 is also required during early embryonic development and for the maintenance of normal higher order polytene chromosome structure in third instar larvae.;Our studies also showed that JIL-1 is involved in the histone H3 Ser10 phosphorylation signaling pathway. The JIL-1 immunocomplex can phosphorylate the Ser10 site in a synthetic H3 N-terminal peptide in vitro. In vivo, Ser10 phosphorylation levels in the third instar larvae of JIL-1 mutants are dramatically reduced. In addition, the decreased H3 Ser10 phosphorylation level can be restored with a GFP-JIL-1 transgene. Moreover, the phosphorylated H3 Ser10 is elevated and colocalized with JIL-1 on the male X chromosome.;Thus, our data suggest a model whereby JIL-1 is involved in a signaling pathway that regulates histone H3 Ser10 phosphorylation in D. melanogaster , which is required to maintain the appropriate higher order chromatin structure to facilitate chromatin functions, such as gene expression, dosage compensation, and so on.
Digital Repository @ Iowa State University, http://lib.dr.iastate.edu
Wang, Yanming, "Drosophila JIL-1 kinase mediates histone H3 Ser10 phosphorylation, maintains higher order chromatin structure, and is implicated in dosage compensation " (2001). Retrospective Theses and Dissertations. 1087.