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

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\u27s kinase activity and have equal importance. The CTD is sufficient for JIL\u27s 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

Investigation of Travel and Activity Patterns Using Location-based Social Network Data : A Case Study of Active Mobile Social Media Users

Due to its relatively high availability and low cost, location-based social network (LBSN) (e.g., Foursquare) data (a popular type of volunteered geographic information) seem to be an alternative or complement to survey data in the study of travel behavior and activity analysis. Illustrating this situation, recently, a number of studies attempted to use LBSN data (e.g., Foursquare check-ins) to investigate patterns of human travel and activity. Of particular note is that compared to other individual-level characteristics of users, such as age, profession, education, income and so forth, gender is relatively highly available in the profiles of Foursquare users. Moreover, considering gender differences in travel and activity analysis is a popular research topic and is helpful in better understanding the changes in women’s roles in family, labor force participation, society and so forth. Therefore, this paper empirically investigates how gender influences the travel and activity patterns of active local Foursquare users in New York City. Empirical investigations of gender differences in travel and activity patterns are conducted at both the individual and aggregate level. The empirical results reveal that there are gender differences in the travel and activity patterns of active local users in New York City at both the individual and aggregate level. Finally, the results of the empirical study and the extent to which LBSN data can be exploited to produce travel diary data are discussed

Histone H3S10 phosphorylation by the JIL-1 kinase in pericentric heterochromatin and on the fourth chromosome creates a composite H3S10phK9me2 epigenetic mark

The JIL-1 kinase mainly localizes to euchromatic interband regions of polytene chromosomes and is the kinase responsible for histone H3S10 phosphorylation at interphase in Drosophila. However, recent findings raised the possibility that the binding of some H3S10ph antibodies may be occluded by the H3K9me2 mark obscuring some H3S10 phosphorylation sites. Therefore, we have characterized an antibody to the epigenetic H3S10phK9me2 double mark as well as three commercially available H3S10ph antibodies. The results showed that for some H3S10ph antibodies their labeling indeed can be occluded by the concomitant presence of the H3K9me2 mark. Furthermore, we demonstrate that the double H3S10phK9me2 mark is present in pericentric heterochromatin as well as on the fourth chromosome of wild-type polytene chromosomes but not in preparations from JIL-1 or Su(var)3-9 null larvae. Su(var)3-9 is a methyltransferase mediating H3K9 dimethylation. Furthermore, the H3S10phK9me2 labeling overlapped with that of the non-occluded H3S10ph antibodies as well as with H3K9me2 antibody labeling. Interestingly, when a Lac-I-Su(var)3-9 transgene is overexpressed, it upregulates H3K9me2 dimethylation on the chromosome arms creating extensive ectopic H3S10phK9me2 marks suggesting that the H3K9 dimethylation occurred at euchromatic H3S10ph sites. This is further supported by the finding that under these conditions euchromatic H3S10ph labeling by the occluded antibodies was abolished. Thus, our findings indicate a novel role for the JIL-1 kinase in epigenetic regulation of heterochromatin in the context of the chromocenter and fourth chromosome by creating a composite H3S10phK9me2 mark together with the Su(var)3-9 methyltransferase

The epigenetic H3S10 phosphorylation mark is required for counteracting heterochromatic spreading and gene silencing in Drosophila melanogaster

The JIL-1 kinase localizes specifically to euchromatin interband regions of polytene chromosomes and is the kinase responsible for histone H3S10 phosphorylation at interphase. Genetic interaction assays with strong JIL-1 hypomorphic loss-of-function alleles have demonstrated that the JIL-1 protein can counterbalance the effect of the major heterochromatin components on position-effect variegation (PEV) and gene silencing. However, it is unclear whether this was a causative effect of the epigenetic H3S10 phosphorylation mark, or whether the effect of the JIL-1 protein on PEV was in fact caused by other functions or structural features of the protein. By transgenically expressing various truncated versions of JIL-1, with or without kinase activity, and assessing their effect on PEV and heterochromatic spreading, we show that the gross perturbation of polytene chromosome morphology observed in JIL-1 null mutants is unrelated to gene silencing in PEV and is likely to occur as a result of faulty polytene chromosome alignment and/or organization, separate from epigenetic regulation of chromatin structure. Furthermore, the findings provide evidence that the epigenetic H3S10 phosphorylation mark itself is necessary for preventing the observed heterochromatic spreading independently of any structural contributions from the JIL-1 protein

H2Av facilitates H3S10 phosphorylation but is not required for heat shock-induced chromatin decondensation or transcriptional elongation

A model has been proposed in which JIL-1 kinase-mediated H3S10 and H2Av phosphorylation is required for transcriptional elongation and heat shock-induced chromatin decondensation. However, here we show that although H3S10 phosphorylation is indeed compromised in the H2Av null mutant, chromatin decondensation at heat shock loci is unaffected in the absence of JIL-1 as well as of H2Av and that there is no discernable decrease in the elongating form of RNA polymerase II in either mutant. Furthermore, mRNA for the major heat shock protein Hsp70 is transcribed at robust levels in both H2Avand JIL-1 null mutants. Using a different chromatin remodeling paradigm that is JIL-1 dependent, we provide evidence that ectopic tethering of JIL-1 and subsequent H3S10 phosphorylation recruits PARP-1 to the remodeling site independently of H2Av phosphorylation. These data strongly suggest that H2Av or H3S10 phosphorylation by JIL-1 is not required for chromatin decondensation or transcriptional elongation in Drosophila

Wear-resistant CrCoNi nanocrystalline film via friction-driven surface segregation

Revealing the frictional behavior through the lens of structural and chemical evolution is crucial for comprehending the exceptional wear-resistance of alloys with complex composition. Here, we propose that superior wear resistance can be achieved via dynamic surface segregation during sliding at room temperature. This strategy was demonstrated in CrCoNi multi-principal element alloy (MPEA) films with nano-grain structure, which exhibit a remarkably low wear rate that is <50 % of that for their VCoNi counterpart. Such distinct wear behavior is attributed to the specific friction-driven Ni segregation on the CrCoNi surface, which facilitates the preferential oxidation and formation of a nanocomposite protective layer with equiaxed nanograins uniformly embedded in an amorphous matrix. This wear-induced unique microstructure accommodates sliding-induced plastic deformation against damage and is responsible for the superior wear-resistance. Having revealed these fundamental mechanisms by experiment and simulation, this study provides a brand-new perception for designing self-adaptive MPEA surfaces. This involves adjusting the evolution of deformation layers with specific structure and chemistry, precisely engineered for tribological applications

Genome-wide analysis of regulation of gene expression and H3K9me2 distribution by JIL-1 kinase mediated histone H3S10 phosphorylation in Drosophila

In this study we have determined the genome-wide relationship of JIL-1 kinase mediated H3S10 phosphorylation with gene expression and the distribution of the epigenetic H3K9me2 mark. We show in wild-type salivary gland cells that the H3S10ph mark is predominantly enriched at active genes whereas the H3K9me2 mark is largely associated with inactive genes. Comparison of global transcription profiles in salivary glands from wild-type and JIL-1 null mutant larvae revealed that the expression levels of 1539 genes changed at least 2-fold in the mutant and that a substantial number (49%) of these genes were upregulated whereas 51% were downregulated. Furthermore, the results showed that downregulation of genes in the mutant was correlated with higher levels or acquisition of the H3K9me2 mark whereas upregulation of a gene was correlated with loss of or diminished H3K9 dimethylation. These results are compatible with a model where gene expression levels are modulated by the levels of the H3K9me2 mark independent of the state of the H3S10ph mark, which is not required for either transcription or gene activation to occur. Rather, H3S10 phosphorylation functions to indirectly maintain active transcription by counteracting H3K9 dimethylation and gene silencing

JASPer controls interphase histone H3S10 phosphorylation by chromosomal kinase JIL-1 in Drosophila

In flies, the chromosomal kinase JIL-1 is responsible for most interphase histone H3S10 phosphorylation and has been proposed to protect active chromatin from acquiring heterochromatic marks, such as dimethylated histone H3K9 (H3K9me2) and HP1. Here, we show that JIL-1's targeting to chromatin depends on a PWWP domain-containing protein JASPer (JIL-1 Anchoring and Stabilizing Protein). JASPer-JIL-1 (JJ)-complex is the major form of kinase in vivo and is targeted to active genes and telomeric transposons via binding of the PWWP domain of JASPer to H3K36me3 nucleosomes, to modulate transcriptional output. JIL-1 and JJ-complex depletion in cycling cells lead to small changes in H3K9me2 distribution at active genes and telomeric transposons. Finally, we identify interactors of the endogenous JJ-complex and propose that JIL-1 not only prevents heterochromatin formation but also coordinates chromatin-based regulation in the transcribed part of the genome