PWWP-mutants of the transcriptional cofactor JASPer divert promoter and enhancer activities and suppress position effect variegation in Drosophila [ChIP-Seq]

Through a new Su(var) screen, we identified Su140 and Su113 as very strong Su(var) mutants that are epistatic over Su(var)3-9 in the In(1)wm4h PEV rearrangement. Both Su140 and Su113 encode point mutations in the PWWP domain of the transcriptional cofactor JASPer that has described functions in protecting gene activity in euchromatin.

In JasperSu140/Su140 and JasperSu113/Su113 nuclear cycle (NC14) mutant embryos, heterochromatic marks (H3K9me2 and H3K9me3) are reduced, while activating histone modifications (H3K4me1 and H3K27ac) become enriched at heterochromatin. Whereas epitope-tagged wild-type JASPer accumulates over H3K36me3-positive regions in gene bodies, mutant JASPerSu140 is redistributed to cis-regulatory motifs (CRM) in promoters and enhancers.