Gene name - JIL-1 kinase G> Synonyms - 2Ab17
Cytological map position - Function - signal transduction
Keywords - chromatin, dosage compensation
Symbol
FBgn0020412
Classification - protein serine/threonine inase
Cellular location - nuclear
| Recent literature | Li, Y., Wang, C., Cai, W., Sengupta, S., Zavortink, M., Deng, H., Girton, J., Johansen, J. and Johansen, K. M. (2017). H2Av facilitates H3S10 phosphorylation but is not required for heat shock-induced chromatin decondensation or transcriptional elongation. Development 144(18): 3232-3240. PubMed ID: 28807902
Summary: 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, this study shows 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 H2Av and JIL-1 null mutants. Using a different chromatin remodeling paradigm that is JIL-1 dependent, evidence is provided 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. |
Albig, C., Wang, C., Dann, G. P., Wojcik, F., Schauer, T., Krause, S., Maenner, S., Cai, W., Li, Y., Girton, J., Muir, T. W., Johansen, J., Johansen, K. M., Becker, P. B. and Regnard, C. (2019). JASPer controls interphase histone H3S10 phosphorylation by chromosomal kinase JIL-1 in Drosophila. Nat Commun 10(1): 5343. PubMed ID: 31767855
Summary: 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. This study shows that JIL-1's targeting to chromatin depends on a PWWP domain-containing protein JASPer (JIL-1 Anchoring and Stabilizing Protein; CG7946). 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, interactors of the endogenous JJ-complex were identified, and it is proposed that JIL-1 not only prevents heterochromatin formation but also coordinates chromatin-based regulation in the transcribed part of the genome. |
Dou, K., Liu, Y., Zhang, Y., Wang, C., Huang, Y. and Zhang, Z. Z. (2020). Drosophila P75 safeguards oogenesis by preventing H3K9me2 spreading. J Genet Genomics. PubMed ID: 32499180
Summary: Serving as a host factor for human immunodeficiency virus (HIV) integration, LEDGF/p75 has been under extensive study as a potential target for therapy. However, as a highly conserved protein, its physiological function remains to be thoroughly elucidated. This study characterized the molecular function of dP75, the Drosophila homolog of LEDGF/p75, during oogenesis. dP75 binds to transcriptionally active chromatin with its PWWP domain. The C-terminus integrase-binding domain-containing region of dP75 physically interacts with the histone kinase Jil-1 and stabilizes it in vivo. Together with Jil-1, dP75 prevents the spreading of the heterochromatin mark-H3K9me2-onto genes required for oogenesis and piRNA production. Without dP75, ectopical silencing of these genes disrupts oogenesis, activates transposons, and causes animal sterility. It is proposed that dP75, the homolog of an HIV host factor in Drosophila, partners with and stabilizes Jil-1 to ensure gene expression during oogenesis by preventing ectopic heterochromatin spreading. |
Hodkinson, L. J., Smith, C., Comstra, H. S., ...., Zeng, H., Schmidt, C. A., Rieder, L. E. (2023). A bioinformatics screen reveals hox and chromatin remodeling factors at the Drosophila histone locus. BMC genomic data, 24(1):54 PubMed ID: 37735352
Summary: Cells orchestrate histone biogenesis with strict temporal and quantitative control. To efficiently regulate histone biogenesis, the repetitive Drosophila melanogaster replication-dependent histone genes are arrayed and clustered at a single locus. Regulatory factors concentrate in a nuclear body known as the histone locus body (HLB), which forms around the locus. Historically, HLB factors are largely discovered by chance, and few are known to interact directly with DNA. It is therefore unclear how the histone genes are specifically targeted for unique and coordinated regulation. RESULTS: To expand the list of known HLB factors, we performed a candidate-based screen by mapping 30 publicly available ChIP datasets of 27 unique factors to the Drosophila histone gene array. We identified novel transcription factor candidates, including the Drosophila Hox proteins Ultrabithorax (Ubx), Abdominal-A (Abd-A), and Abdominal-B (Abd-B), suggesting a new pathway for these factors in influencing body plan morphogenesis. Additionally, six other factors were identified that target the histone gene array: JIL-1, hormone-like receptor 78 (Hr78), the long isoform of female sterile homeotic (1) (fs(1)h) as well as the general transcription factors TBP associated factor 1 (TAF-1), Transcription Factor IIB (TFIIB), and Transcription Factor IIF (TFIIF). This foundational screen provides several candidates for future studies into factors that may influence histone biogenesis. Further, this study emphasizes the powerful reservoir of publicly available datasets, which can be mined as a primary screening technique. |
Jayakrishnan, M., Havlova, M., Veverka, V., Regnard, C., Becker, P. B. (2025). Genomic context-dependent histone H3K36 methylation by three Drosophila methyltransferases and implications for dedicated chromatin readers. Nucleic Acids Res, 53(6) PubMed ID: 40164442
Summary: Methylation of histone H3 at lysine 36 (H3K36me3) marks active chromatin. The mark is interpreted by epigenetic readers that assist transcription and safeguard chromatin fiber integrity. In Drosophila, the chromodomain protein MSL3 binds H3K36me3 at X-chromosomal genes to implement dosage compensation. The PWWP-domain protein JASPer recruits the JIL1 kinase to active chromatin on all chromosomes. Because depletion of K36me3 had variable, locus-specific effects on the interactions of those readers,K36 methylation was systematically studied in a defined cellular model. Contrasting prevailing models, K36me1, K36me2, and K36me3 were each found to contribute to distinct chromatin states. Monitoring the changing K36 methylation landscape upon depletion of the three methyltransferases Set2, NSD, and Ash1 revealed local, context-specific methylation signatures. Each methyltransferase governs K36 methylation in dedicated genomic regions, with minor overlaps. Set2 catalyzes K36me3 predominantly at transcriptionally active euchromatin. NSD places K36me2/3 at defined loci within pericentric heterochromatin and on weakly transcribed euchromatic genes. Ash1 deposits K36me1 at putative enhancers. The mapping of MSL3 and JASPer suggested that they bind K36me2 in addition to K36me3, which was confirmed by direct affinity measurement. This dual specificity attracts the readers to a broader range of chromosomal locations and increases the robustness of their actions. |
Jin, Z., Meng, Z., Liu, Y., Li, C., Zhang, X., Yin, Y., Gao, G., Dou, K., Huang, Y. (2025). Structural basis of thymidine-rich DNA recognition by Drosophila P75 PWWP domain Commun Biol, 8(1):445 PubMed ID: 40089621
Summary: Drosophila P75 [JIL-1 anchoring and stabilizing protein (dP75)], a homolog of the human LEDGF/p75, is crucial for oogenesis by recruiting the histone kinase Jil-1 to euchromatin and impeding H3K9me2 spreading. Like LEDGF, dP75 binds transcriptionally active chromatin, but its precise mechanism remains unclear. This study shows that its PWWP domain prefers binding to thymidine-rich DNA over GC-rich sequences. Crystal structures both in apo and ssDNA-bound states, reveal a domain-swapped homodimer. The aromatic cage, known to recognize histone methyllysine, also engages thymine. Mutations in this cage mimic dP75 knockout phenotypes, including impaired chromatin binding, transposon upregulation, and female sterility. Although dP75 maintains chromatin-bound in H3K36A mutant flies, alterations in the aromatic cage disrupt this localization, underscoring its role in DNA binding. These findings reveal how dP75 targets euchromatin through a PWWP domain that integrates histone reading and nucleotide recognition, advancing understanding of PWWP domains. |
A monoclonal antibody, mAb2A, detects a protein (Johansen, 1996a; Johansen, 1996b) that is chromosomally localized throughout the cell cycle (Jin, 1999). JIL-1, found to be the protein detected by mAb2A, is a chromosomal kinase that is upregulated almost twofold on the male X chromosome in Drosophila. Phylogenetic analysis suggests that JIL-1 together with the related human MSKs define a
separate family of tandem kinases. JIL-1 undergoes autophosphorylation and phosphorylation of Histone H3 in vitro. It is suggested that JIL-1 is part of the dosage compensation apparatus. JIL-1 colocalizes and
physically interacts with male specific lethal (MSL) dosage compensation complex
proteins. Ectopic expression of the MSL complex directed by MSL2 in
females causes a concomitant upregulation of JIL-1 to the female X that is
abolished in msl mutants unable to assemble the complex. Thus, these results
strongly indicate JIL-1 associates with the MSL complex and further suggests that
JIL-1 functions in signal transduction pathways regulating chromatin structure (Jin, 1999 and 2000).
P>JIL-1's distribution pattern was analyzed in confocal images of larval polytene chromosomes. JIL-1 localizes to hundreds of sites along the polytene chromosome that correspond to interband regions. Since interbands arise from partial unfolding of the 30 nm chromatin fiber and
have been proposed to be the sites of actively transcribed genes, these findings suggest that JIL-1 may be involved in gene activity potentially by regulation of chromatin structure via histone phosphorylation. However, JIL-1 is not required at all locations of decondensed chromatin since there are interband regions that do not show JIL-1 labeling. The expression of JIL-1 on female and male X chromosomes was tested in relation to JIL-1 expression on autosomes. In female polytene
squashes there is no significant difference between autosomal and X chromosome staining intensity, whereas in males, a
highly statistically significant difference is found between autosomal and X-chromosomal staining
intensities. There is an almost 2-fold increase in the level of JIL-1 on the Drosophila male X chromosome compared to autosomes, which
correlates well with the roughly 2-fold increased transcription level on this chromosome due to dosage compensation mechanisms. This finding also raises the intriging possiblity that JIL-1 plays a functional role in dosage compensation (Jin, 1999).
P>n an effort to determine the molecular basis for dosage compensation in Drosophila, a number of genetic screens were performed that have identified several
genes necessary for achieving equal levels of most X-linked transcription. The products of these genes
assemble into a complex termed MSL (male specific lethal) that is thought to be responsible for targeting a histone acetyltransferase that acetylates histone H4
(H4Ac16) to the upregulated male X chromosome, which in turn leads to altered chromatin structure (Smith, 2000). The MSL holocomplex is known to
include MSL1, a novel acidic protein; MSL2, a RING finger protein; MSL3, a chromodomain protein; MLE, an RNA helicase; MOF, a histone
acetyltransferase, and two nontranslated RNAs, roX1 and roX2. The MSL complex
preferentially associates at hundreds of sites on the male X but fails to assemble in females due to a Sex lethal-regulated block in translation of the MSL2
subunit. The MSL complex colocalizes with the H4Ac16 pattern on the male X chromosome, and absence of any of
the MSL complex subunits prevents both MSL complex assembly as well as the enhanced H4Ac16 modification on the male X chromosome. Furthermore, studies have shown that ectopic expression of MSL2 in females results in formation and targeting of the
MSL complex to both female X chromosomes with a concomitant upregulation of H4Ac16 levels (Jin, 2000 and references therein).
In onat to the other MSL complex proteins, JIL-1 is also present in female chromosomes and male autosomes (Jin, 1999), all of which are void of
MSL complexes. Future experiments will determine whether JIL-1's more general distribution on the autosomes and on the female
X chromosomes may reflect JIL-1's participation in other transcriptional regulator complexes. The deployment of certain proteins into several different chromatin
remodeling complexes is emerging as a common theme in the composition of various chromatin remodeling machines and may be a way to accomplish
hierarchical levels of gene regulation. It has been shown that JIL-1 associates with at least one known chromatin remodeling
machine, the MSL complex, suggesting a direct link between the JIL-1 kinase and the signal transduction pathways regulating transcription and chromatin
structure (Jin, 2000).
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A monoclonal antibody, mA2A was used to screen a lambda gt11 genomic Drosophila expression library. A partial clone identified in this expression screen was subsequently used to probe embryonic and ovary-specific cDNA libraries, resulting in isolation of several overlapping cDNAs from both developmental stages spanning approximately 6.5 kb. The encoded protein contains two tandemly arranged serine/threonine kinase domains. Based on this tandem kinase domain structure, which is reminiscent of the JAK family of tyrosine kinases, the protein has been named JIL-1. The NH2-terminal domain contains an asparagine-rich stretch (9 out of 10 residues) and an alanine-rich stretch (16 residues). In addition, JIL-1 contains a bipartite nuclear localization signal starting at position 58. Three regions characterized by a low hydrophobicity index and high proline, glutamic acid, aspartic acid, serine, and threonine content are similar to PEST sequences that have been implicated in targeting proteins for rapid turnover (Jin, 1999).
The two kinase domains o J-, KDI and KDII, were compared with all sequences in the current databases in order to identify the most related sequences. KDII is not closely related to any other kinase family; however, KDI has the highest sequence identity with the first kinase domain of a novel protein tandem kinase in human reported in two recent studies called mitogen- and stress-activated kinase, MSK1 (Deak, 1998), or RSK-like protein kinase, RLPK. Whereas JIL-1 is 63% identical in KDI to MSK1, it is only 47% identical to Drosophila RSK. In KDII, JIL-1 is 32% and 28% identical to the second kinase domain in MSK1 and Drosophila RSK, respectively, a level of shared residues reflecting the general level of conserved features among kinase domains. Compared to these other tandem kinases, JIL-1 shows extended NH2- and COOH-terminal domains. To further determine the evolutionary relationship between JIL-1 and other protein kinases, phylogenetic trees were constructed based on maximum parsimony. The phylogenetic analysis indicates that JIL-1 is grouped with 95% bootstrap support with human MSK1 and MSK2 in a monophyletic clade that is distinct from the RSK, S6, and RAC kinase families and their Drosophila homologs. Consequently, these data suggest that JIL-1 is the Drosophila representative of a novel tandem serine/threonine kinase family, which it defines together with MSK1 and MSK2. Interestingly, this phylogenetic analysis also suggests that the S6 kinases, which are single-domain kinases, may have evolved from tandem kinases by a deletion of the second kinase domain (Jin, 1999).
date revised: 21 March 2026
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