Global analysis of the relationship between JIL-1 kinase and transcription

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. © 2011 regnard et al.