title: Global analysis of the relationship between JIL-1 kinase and transcription.
abstract: The ubiquitous tandem kinase JIL-1 is essential for Drosophila development. Its role in defining decondensed domains of larval polytene chromosomes is well established, but its involvement in transcription regulation has remained controversial. For a first comprehensive molecular characterisation of JIL-1, we generated a high-resolution, chromosome-wide interaction profile of the kinase in Drosophila cells and determined its role in transcription. JIL-1 binds active genes along their entire length. The presence of the kinase is not proportional to average transcription levels or polymerase density. Comparison of JIL-1 association with elongating RNA polymerase and a variety of histone modifications suggests two distinct targeting principles. A basal level of JIL-1 binding can be defined that correlates best with the methylation of histone H3 at lysine 36, a mark that is placed co-transcriptionally. The additional acetylation of H4K16 defines a second state characterised by approximately twofold elevated JIL-1 levels, which is particularly prominent on the dosage-compensated male X chromosome. Phosphorylation of the histone H3 N-terminus by JIL-1 in vitro is compatible with other tail modifications. In vivo, phosphorylation of H3 at serine 10, together with acetylation at lysine 14, creates a composite histone mark that is enriched at JIL-1 binding regions. Its depletion by RNA interference leads to a modest, but significant, decrease of transcription from the male X chromosome. Collectively, the results suggest that JIL-1 participates in a complex histone modification network that characterises active, decondensed chromatin. We hypothesise that one specific role of JIL-1 may be to reinforce, rather than to establish, the status of active chromatin through the phosphorylation of histone H3 at serine 10.
authors.affiliation: Adolf-Butenandt-Institute and Centre for Integrated Protein Science (CiPSM), Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Catherine
authors.initials: C
authors.lastname: Regnard
authors.forename: Tobias
authors.initials: T
authors.lastname: Straub
authors.forename: Angelika
authors.initials: A
authors.lastname: Mitterweger
authors.forename: Ina K
authors.initials: IK
authors.lastname: Dahlsveen
authors.forename: Viola
authors.initials: V
authors.lastname: Fabian
authors.forename: Peter B
authors.initials: PB
authors.lastname: Becker
mesh_terms: D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D004303:Dosage Compensation, Genetic; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics*; D005260:Female; D017344:Genes, Insect; D017930:Genes, Reporter; D050172:Genes, X-Linked; D056426:Genetic Loci; D006657:Histones / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D012319:RNA Polymerase II / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014960:X Chromosome / Q000378:metabolism
chemical_list: D002843:Chromatin; D029721:Drosophila Proteins; D006657:Histones; C507306:JIL-1 protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D012319:RNA Polymerase II